ribociclib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
cyclin dependant kinase inhibitors	5218	1211441-98-3

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: ribociclib ribociclib succinate LEE011 LEE 011 kisqali LEE011-BBA LEE011A	Ribociclib is an inhibitor of cyclin-dependent kinase (CDK) 4 and 6. These kinases are activated upon binding to D-cyclins and play a crucial role in signaling pathways which lead to cell cycle progression and cellular proliferation. The cyclin D-CDK4/6 complex regulates cell cycle progression through phosphorylation of the retinoblastoma protein (pRb). In vitro, ribociclib decreased pRb phosphorylation leading to arrest in the G1 phase of the cell cycle and reduced cell proliferation in breast cancer cell lines. In vivo, treatment with single agent ribociclib in a rat xenograft model with human tumor cells led to decreased tumor volumes, which correlated with inhibition of pRb phosphorylation. In studies using patient-derived estrogen receptor positive breast cancer xenograft models, combination of ribociclib and antiestrogen (e.g. letrozole) resulted in increased tumor growth inhibition compared to each drug alone. Molecular weight: 434.55 Formula: C23H30N8O CLOGP: 2.06 LIPINSKI: 0 HAC: 9 HDO: 2 TPSA: 91.21 ALOGS: -3.28 ROTB: 5 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

ribociclib
ribociclib succinate
LEE011
LEE 011
kisqali
LEE011-BBA
LEE011A

Ribociclib is an inhibitor of cyclin-dependent kinase (CDK) 4 and 6. These kinases are activated upon binding to D-cyclins and play a crucial role in signaling pathways which lead to cell cycle progression and cellular proliferation. The cyclin D-CDK4/6 complex regulates cell cycle progression through phosphorylation of the retinoblastoma protein (pRb). In vitro, ribociclib decreased pRb phosphorylation leading to arrest in the G1 phase of the cell cycle and reduced cell proliferation in breast cancer cell lines. In vivo, treatment with single agent ribociclib in a rat xenograft model with human tumor cells led to decreased tumor volumes, which correlated with inhibition of pRb phosphorylation. In studies using patient-derived estrogen receptor positive breast cancer xenograft models, combination of ribociclib and antiestrogen (e.g. letrozole) resulted in increased tumor growth inhibition compared to each drug alone.

Molecular weight: 434.55
Formula: C23H30N8O
CLOGP: 2.06
LIPINSKI: 0
HAC: 9
HDO: 2
TPSA: 91.21
ALOGS: -3.28
ROTB: 5

Status: ONP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
0.45	g	O

ADMET properties:

Property	Value	Reference
S (Water solubility)	0.80 mg/mL	Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Bocci G, Oprea TI, Benet LZ

Approvals:

Date	Agency	Company	Orphan
Aug. 22, 2017	EMA	Novartis Europharm Ltd
March 13, 2017	FDA	NOVARTIS PHARMS CORP

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Neutropenia	3221.16	19.61	1785	40867	173220	63273150
Malignant neoplasm progression	1653.94	19.61	892	41760	81229	63365141
Leukopenia	1337.34	19.61	760	41892	76530	63369840
Metastases to bone	1127.56	19.61	451	42201	20568	63425802
Metastases to liver	824.91	19.61	374	42278	23265	63423105
Electrocardiogram QT prolonged	715.46	19.61	464	42188	59066	63387304
Aspartate aminotransferase increased	399.61	19.61	391	42261	89886	63356484
Alanine aminotransferase increased	385.73	19.61	409	42243	103361	63343009
Metastases to lung	377.05	19.61	180	42472	12570	63433800
Hepatotoxicity	359.24	19.61	253	42399	36788	63409582
Carbohydrate antigen 15-3 increased	355.12	19.61	98	42554	1350	63445020
Drug ineffective	343.19	19.61	138	42514	1044627	62401743
Neutrophil count decreased	332.71	19.61	287	42365	56119	63390251
White blood cell count decreased	311.95	19.61	424	42228	138680	63307690
Thrombocytopenia	293.42	19.61	430	42222	150727	63295643
Anaemia	280.49	19.61	612	42040	292818	63153552
Gamma-glutamyltransferase increased	274.54	19.61	208	42444	33823	63412547
Bone pain	240.33	19.61	236	42416	54405	63391965
Off label use	237.77	19.61	79	42573	674383	62771987
Bone lesion	236.93	19.61	103	42549	5778	63440592
Metastases to lymph nodes	234.58	19.61	113	42539	8045	63438325
General physical health deterioration	221.23	19.61	445	42207	200957	63245413
Skin hypopigmentation	219.45	19.61	59	42593	732	63445638
Pleural effusion	214.68	19.61	288	42364	92922	63353448
Blood creatinine increased	204.71	19.61	273	42379	87571	63358799
Polyneuropathy	195.58	19.61	122	42530	14467	63431903
Tumour marker increased	191.23	19.61	84	42568	4831	63441539
Transaminases increased	179.59	19.61	157	42495	31210	63415160
Liver function test increased	169.57	19.61	155	42497	32656	63413714
Nausea	158.94	19.61	1047	41605	853424	62592946
Eastern Cooperative Oncology Group performance status worsened	155.05	19.61	50	42602	1204	63445166
PIK3CA-activated mutation	146.52	19.61	46	42606	1013	63445357
Hot flush	142.81	19.61	174	42478	50985	63395385
Drug hypersensitivity	137.63	19.61	22	42630	310665	63135705
Carcinoembryonic antigen increased	130.85	19.61	48	42604	1717	63444653
Metastases to pleura	128.32	19.61	46	42606	1539	63444831
Breast cancer metastatic	127.97	19.61	87	42565	11931	63434439
Metastases to spine	127.93	19.61	56	42596	3193	63443177
Blood alkaline phosphatase increased	126.24	19.61	150	42502	42817	63403553
Arthropathy	126.15	19.61	8	42644	234784	63211586
Condition aggravated	123.49	19.61	58	42594	402159	63044211
Erysipelas	118.46	19.61	71	42581	7834	63438536
Metastasis	117.03	19.61	61	42591	5136	63441234
Ascites	111.19	19.61	137	42515	40591	63405779
Joint swelling	110.60	19.61	41	42611	327625	63118745
Blood bilirubin increased	109.66	19.61	130	42522	37010	63409360
Fatigue	106.78	19.61	984	41668	887044	62559326
Glossodynia	99.43	19.61	5	42647	178871	63267499
Product use issue	99.00	19.61	15	42637	220505	63225865
Spinal pain	98.66	19.61	77	42575	13062	63433308
Treatment failure	95.42	19.61	11	42641	199032	63247338
Metastases to central nervous system	94.53	19.61	75	42577	13030	63433340
Hepatic lesion	90.07	19.61	50	42602	4775	63441595
Sinusitis	87.90	19.61	22	42630	226631	63219739
Death	84.32	19.61	483	42169	373898	63072472
Swelling	80.97	19.61	42	42610	275336	63171034
Pneumonitis	79.72	19.61	108	42544	35114	63411256
Bone marrow infiltration	79.40	19.61	26	42626	658	63445712
Glomerular filtration rate decreased	78.36	19.61	68	42584	13373	63432997
Musculoskeletal stiffness	75.40	19.61	16	42636	184602	63261768
Osteonecrosis of jaw	73.94	19.61	104	42548	35019	63411351
Hypotension	73.80	19.61	46	42606	272558	63173812
Intentional product use issue	72.93	19.61	3	42649	127889	63318481
Lymphoedema	71.92	19.61	61	42591	11631	63434739
Disease progression	68.94	19.61	210	42442	122548	63323822
Decreased immune responsiveness	68.24	19.61	42	42610	4859	63441511
Vitiligo	68.18	19.61	28	42624	1361	63445009
Dry skin	67.47	19.61	130	42522	56757	63389613
Hypertensive crisis	67.10	19.61	66	42586	15220	63431150
Hydrothorax	64.17	19.61	24	42628	907	63445463
Electrocardiogram PR shortened	64.10	19.61	18	42634	265	63446105
Pyelitis	63.67	19.61	17	42635	205	63446165
Decreased appetite	62.51	19.61	333	42319	250719	63195651
Wound	61.09	19.61	17	42635	163246	63283124
Jaundice	60.66	19.61	86	42566	29165	63417205
Metastases to skin	60.12	19.61	27	42625	1636	63444734
Haemoglobin decreased	59.70	19.61	224	42428	145261	63301109
Lacrimation increased	58.89	19.61	71	42581	20560	63425810
Asthma	58.80	19.61	8	42644	127553	63318817
COVID-19	58.45	19.61	188	42464	112915	63333455
Hypocalcaemia	58.18	19.61	88	42564	31625	63414745
Taste disorder	58.14	19.61	58	42594	13604	63432766
Blood lactate dehydrogenase increased	57.11	19.61	74	42578	23042	63423328
Toxicity to various agents	56.23	19.61	50	42602	247200	63199170
Anisocytosis	54.98	19.61	20	42632	698	63445672
Therapeutic product effect incomplete	54.98	19.61	9	42643	125047	63321323
Breast cancer recurrent	54.91	19.61	35	42617	4306	63442064
Weight increased	53.24	19.61	58	42594	260734	63185636
Hepatic cytolysis	52.34	19.61	58	42594	15349	63431021
Skin toxicity	52.27	19.61	35	42617	4679	63441691
Drug intolerance	51.36	19.61	80	42572	308581	63137789
Neoplasm	50.76	19.61	41	42611	7304	63439066
Loss of personal independence in daily activities	50.23	19.61	4	42648	97286	63349084
Calcium deficiency	49.78	19.61	21	42631	1093	63445277
Hypersensitivity	49.51	19.61	75	42577	292610	63153760
Abdominal discomfort	48.92	19.61	88	42564	320797	63125573
Elliptocytosis	48.59	19.61	11	42641	62	63446308
Isosthenuria	48.12	19.61	12	42640	108	63446262
Haematotoxicity	47.84	19.61	44	42608	9332	63437038
Constipation	47.14	19.61	285	42367	224658	63221712
Discomfort	47.01	19.61	27	42625	167347	63279023
Therapy partial responder	46.74	19.61	46	42606	10612	63435758
Hepatic failure	46.65	19.61	85	42567	35571	63410799
Lymphocyte count decreased	45.92	19.61	77	42575	30180	63416190
Injection site pain	45.86	19.61	15	42637	129785	63316585
Arthritis	45.40	19.61	11	42641	115910	63330460
Helicobacter infection	44.76	19.61	5	42647	92780	63353590
Hormone receptor positive HER2 negative breast cancer	44.55	19.61	12	42640	150	63446220
Irritable bowel syndrome	43.65	19.61	3	42649	82409	63363961
Urticaria	42.11	19.61	30	42622	165772	63280598
Tumour marker abnormal	42.07	19.61	14	42638	373	63445997
Alopecia	41.68	19.61	377	42275	337159	63109211
Onychoclasis	41.46	19.61	34	42618	6188	63440182
Urinary tract inflammation	41.17	19.61	9	42643	42	63446328
Blood cholesterol increased	40.81	19.61	7	42645	94025	63352345
Lower respiratory tract infection	40.63	19.61	19	42633	132288	63314082
Bladder hypertrophy	39.88	19.61	12	42640	228	63446142
Lymphadenopathy	39.74	19.61	83	42569	38375	63407995
Aspartate aminotransferase abnormal	39.63	19.61	18	42634	1120	63445250
Concomitant disease aggravated	39.35	19.61	39	42613	9073	63437297
Metastases to peritoneum	39.24	19.61	26	42626	3416	63442954
Hepatic echinococciasis	39.14	19.61	9	42643	55	63446315
Psoriasis	38.80	19.61	6	42646	86951	63359419
Electrocardiogram QT interval abnormal	38.62	19.61	11	42641	171	63446199
Intentional overdose	38.41	19.61	3	42649	74149	63372221
Calcification metastatic	38.32	19.61	11	42641	176	63446194
Loss of consciousness	37.78	19.61	16	42636	118105	63328265
Hepatobiliary disease	37.76	19.61	13	42639	385	63445985
Wheezing	37.57	19.61	9	42643	95586	63350784
Red blood cell count decreased	36.62	19.61	83	42569	40562	63405808
Second primary malignancy	36.14	19.61	35	42617	7918	63438452
Product dose omission issue	35.92	19.61	64	42588	234249	63212121
Fall	35.82	19.61	139	42513	392195	63054175
Cardiac failure congestive	35.75	19.61	9	42643	92424	63353946
Tumour pain	35.63	19.61	18	42634	1419	63444951
Seizure	35.01	19.61	23	42629	132611	63313759
Breast pain	34.97	19.61	36	42616	8762	63437608
Overdose	34.60	19.61	17	42635	115061	63331309
Monocyte count decreased	33.98	19.61	20	42632	2133	63444237
Haematocrit decreased	33.97	19.61	79	42573	39261	63407109
Back pain	33.58	19.61	297	42355	263848	63182522
Atrial fibrillation	33.38	19.61	161	42491	116475	63329895
Neutrophil count abnormal	33.34	19.61	22	42630	2870	63443500
Confusional state	33.22	19.61	68	42584	236312	63210058
Basophil count increased	32.89	19.61	15	42637	942	63445428
Metastases to bone marrow	32.17	19.61	12	42640	450	63445920
Metastases to pelvis	31.95	19.61	12	42640	459	63445911
Resorption bone increased	31.71	19.61	16	42636	1258	63445112
Oxygen saturation decreased	31.70	19.61	10	42642	88575	63357795
Mean cell volume increased	31.51	19.61	23	42629	3528	63442842
CYP3A4 polymorphism	31.32	19.61	8	42644	80	63446290
Cornea verticillata	31.30	19.61	9	42643	145	63446225
Dyspnoea exertional	30.91	19.61	100	42552	60202	63386168
Mean cell haemoglobin increased	30.60	19.61	21	42631	2922	63443448
Mucosal inflammation	29.88	19.61	84	42568	46844	63399526
Poikilocytosis	29.86	19.61	9	42643	172	63446198
Coronavirus infection	29.82	19.61	24	42628	4254	63442116
Sinus arrhythmia	29.52	19.61	16	42636	1457	63444913
Gastrointestinal haemorrhage	29.34	19.61	9	42643	81167	63365203
Pain	29.17	19.61	338	42314	740290	62706080
Renal impairment	29.01	19.61	127	42525	88228	63358142
Blood phosphorus decreased	28.97	19.61	24	42628	4429	63441941
Breast mass	28.96	19.61	31	42621	7891	63438479
Blister	28.60	19.61	27	42625	129787	63316583
Injury	28.58	19.61	7	42645	73240	63373130
Suicidal ideation	28.55	19.61	4	42648	62417	63383953
Creatinine renal clearance increased	28.40	19.61	12	42640	627	63445743
Depressed level of consciousness	28.34	19.61	4	42648	62074	63384296
Joint neoplasm	28.07	19.61	7	42645	63	63446307
Malignant pleural effusion	28.06	19.61	19	42633	2587	63443783
Hepatic cyst	27.89	19.61	25	42627	5129	63441241
Rouleaux formation	27.81	19.61	6	42646	26	63446344
Suicide attempt	27.64	19.61	4	42648	60914	63385456
Radiation oesophagitis	27.60	19.61	10	42642	345	63446025
Soft tissue neoplasm	27.23	19.61	7	42645	72	63446298
Somnolence	27.20	19.61	49	42603	178636	63267734
Metastases to thorax	27.14	19.61	9	42643	237	63446133
Adverse drug reaction	26.79	19.61	10	42642	79704	63366666
Renal failure	26.50	19.61	152	42500	117500	63328870
Dry eye	25.99	19.61	73	42579	40688	63405682
Infection	25.82	19.61	74	42578	229099	63217271
Impaired healing	25.44	19.61	19	42633	102523	63343847
Organ failure	25.30	19.61	18	42634	2653	63443717
Adjusted calcium decreased	25.23	19.61	8	42644	182	63446188
Hospitalisation	24.93	19.61	13	42639	85068	63361302
Hyperchromic anaemia	24.69	19.61	6	42646	48	63446322
Malaise	24.60	19.61	171	42481	415783	63030587
Hypermetabolism	24.48	19.61	8	42644	201	63446169
Adjusted calcium increased	24.37	19.61	5	42647	16	63446354
Wrong technique in product usage process	24.24	19.61	6	42646	62334	63384036
Palmar-plantar erythrodysaesthesia syndrome	24.16	19.61	50	42602	22965	63423405
Bone sequestrum	24.08	19.61	14	42638	1460	63444910
Gingival erythema	23.51	19.61	11	42641	733	63445637
Migraine	23.34	19.61	21	42631	103325	63343045
Chromaturia	23.33	19.61	41	42611	16676	63429694
Osteoporosis	23.32	19.61	5	42647	57333	63389037
Hyperbilirubinaemia	23.06	19.61	33	42619	11281	63435089
Depressed mood	22.76	19.61	69	42583	40122	63406248
Tumour marker decreased	22.73	19.61	6	42646	69	63446301
Metastases to chest wall	22.63	19.61	10	42642	583	63445787
Blood pressure increased	22.44	19.61	47	42605	162015	63284355
Selenium deficiency	22.43	19.61	5	42647	26	63446344
Electrocardiogram abnormal	22.07	19.61	29	42623	9150	63437220
Neoplasm progression	22.02	19.61	64	42588	36364	63410006
Osteolysis	21.91	19.61	17	42635	2857	63443513
Dyspnoea	21.90	19.61	590	42062	660723	62785647
Pleural disorder	21.79	19.61	10	42642	637	63445733
Coma	21.76	19.61	8	42644	64356	63382014
Vomiting	21.69	19.61	510	42142	559107	62887263
Invasive breast carcinoma	21.47	19.61	10	42642	659	63445711
Blood uric acid increased	21.40	19.61	22	42630	5345	63441025
Radiation skin injury	21.03	19.61	11	42641	932	63445438
Muscular weakness	21.00	19.61	31	42621	122322	63324048
Nail avulsion	20.91	19.61	7	42645	190	63446180
Lymphopenia	20.64	19.61	41	42611	18286	63428084
Contusion	20.36	19.61	44	42608	150000	63296370
Cancer pain	20.28	19.61	17	42635	3188	63443182
Sleep disorder	20.11	19.61	108	42544	81458	63364912
Unevaluable event	19.87	19.61	5	42647	51381	63394989
General physical condition abnormal	19.78	19.61	19	42633	4255	63442115

FDA Adverse Event Reporting System (Male)

None

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Neutropenia	1621.47	18.66	1035	23389	286675	79433289
Metastases to bone	876.33	18.66	316	24108	24111	79695853
Malignant neoplasm progression	773.64	18.66	494	23930	135496	79584468
Metastases to liver	560.05	18.66	238	24186	28076	79691888
Electrocardiogram QT prolonged	439.31	18.66	298	24126	90088	79629876
Metastases to lung	314.28	18.66	139	24285	18024	79701940
Carbohydrate antigen 15-3 increased	288.65	18.66	68	24356	1111	79718853
Bone lesion	271.25	18.66	92	24332	5827	79714137
Leukopenia	259.72	18.66	243	24181	116270	79603694
Skin hypopigmentation	246.80	18.66	58	24366	937	79719027
Hepatotoxicity	236.67	18.66	164	24260	51188	79668776
Neutrophil count decreased	205.54	18.66	194	24230	93765	79626199
Alanine aminotransferase increased	188.01	18.66	240	24184	162330	79557634
White blood cell count decreased	182.54	18.66	255	24169	188033	79531931
Aspartate aminotransferase increased	178.44	18.66	216	24208	138425	79581539
Metastases to lymph nodes	177.99	18.66	79	24345	10318	79709646
Tumour marker increased	155.74	18.66	56	24368	4216	79715748
Off label use	138.09	18.66	53	24371	907162	78812802
Breast cancer metastatic	133.38	18.66	61	24363	8541	79711423
Bone pain	129.34	18.66	119	24305	55623	79664341
Carcinoembryonic antigen increased	115.78	18.66	38	24386	2171	79717793
Drug ineffective	111.25	18.66	101	24323	1080812	78639152
Nausea	98.40	18.66	562	23862	956634	78763330
Transaminases increased	92.91	18.66	96	24328	51647	79668317
Gamma-glutamyltransferase increased	92.02	18.66	98	24326	54582	79665382
Metastases to spine	90.91	18.66	38	24386	4286	79715678
Thrombocytopenia	85.87	18.66	225	24199	265034	79454930
Blood creatinine increased	85.78	18.66	163	24261	154894	79565070
Anaemia	84.16	18.66	313	24111	444702	79275262
PIK3CA-activated mutation	83.36	18.66	22	24402	581	79719383
Blood alkaline phosphatase increased	81.48	18.66	99	24325	63565	79656399
Metastasis	79.88	18.66	40	24384	6840	79713124
Pleural effusion	79.48	18.66	152	24272	145110	79574854
Liver function test increased	79.10	18.66	78	24346	39695	79680269
Hepatic lesion	73.63	18.66	38	24386	6921	79713043
Decreased immune responsiveness	73.04	18.66	35	24389	5440	79714524
Metastases to pleura	70.58	18.66	24	24400	1530	79718434
Breast cancer recurrent	68.81	18.66	28	24396	2949	79717015
Fatigue	66.07	18.66	498	23926	929229	78790735
Disease progression	65.44	18.66	162	24262	184200	79535764
Anisocytosis	63.14	18.66	20	24404	1019	79718945
Blood bilirubin increased	61.51	18.66	88	24336	66144	79653820
Condition aggravated	61.32	18.66	39	24385	501085	79218879
Electrocardiogram PR shortened	60.80	18.66	15	24409	300	79719664
Metastases to central nervous system	58.79	18.66	45	24379	16330	79703634
Hypotension	58.50	18.66	31	24393	440286	79279678
Isosthenuria	57.21	18.66	12	24412	111	79719853
Hot flush	57.07	18.66	77	24347	54800	79665164
Vitiligo	56.27	18.66	22	24402	2087	79717877
Elliptocytosis	53.86	18.66	11	24413	88	79719876
Eastern Cooperative Oncology Group performance status worsened	53.20	18.66	21	24403	2044	79717920
Spinal pain	52.42	18.66	41	24383	15351	79704613
Breast mass	52.31	18.66	30	24394	6724	79713240
Therapy partial responder	52.15	18.66	43	24381	17354	79702610
Hepatic cytolysis	49.85	18.66	51	24373	27100	79692864
Hydrothorax	48.87	18.66	18	24406	1450	79718514
Joint swelling	46.91	18.66	15	24409	288631	79431333
Hepatic echinococciasis	46.47	18.66	9	24415	53	79719911
Drug hypersensitivity	46.04	18.66	17	24407	298899	79421065
Haemoglobin decreased	45.90	18.66	161	24263	221958	79498006
Lymphadenopathy	45.46	18.66	68	24356	53179	79666785
Pyelitis	44.97	18.66	12	24412	331	79719633
Back pain	43.16	18.66	196	24228	303984	79415980
Haematotoxicity	41.66	18.66	36	24388	15483	79704481
Resorption bone increased	41.53	18.66	16	24408	1459	79718505
Blood calcium increased	40.48	18.66	30	24394	10370	79709594
Sinusitis	40.13	18.66	6	24418	195495	79524469
Lymphocyte count decreased	39.81	18.66	60	24364	47229	79672735
Hormone receptor positive HER2 negative breast cancer	39.23	18.66	9	24415	130	79719834
Breast cancer	39.15	18.66	50	24374	33731	79686233
Alopecia	38.91	18.66	157	24267	231198	79488766
Fall	38.60	18.66	56	24368	487573	79232391
Cornea verticillata	37.37	18.66	9	24415	162	79719802
Bladder hypertrophy	37.23	18.66	12	24412	647	79719317
Tumour marker abnormal	37.19	18.66	10	24414	284	79719680
Skin toxicity	36.97	18.66	26	24398	8288	79711676
Toxicity to various agents	35.78	18.66	46	24378	421494	79298470
Intentional product use issue	35.40	18.66	3	24421	152109	79567855
Arthropathy	35.08	18.66	6	24418	177105	79542859
Blood phosphorus decreased	34.74	18.66	23	24401	6645	79713319
Dry skin	34.53	18.66	69	24355	67926	79652038
Calcification metastatic	33.82	18.66	8	24416	133	79719831
Red blood cell count decreased	33.68	18.66	62	24362	57451	79662513
Urinary tract inflammation	33.63	18.66	9	24415	251	79719713
Joint neoplasm	33.54	18.66	7	24417	63	79719901
Pruritus	33.44	18.66	221	24203	394427	79325537
Metastases to pelvis	33.14	18.66	11	24413	651	79719313
CYP3A4 polymorphism	32.88	18.66	7	24417	70	79719894
Rouleaux formation	32.51	18.66	6	24418	26	79719938
Hypocalcaemia	32.02	18.66	56	24368	49868	79670096
Hepatic cyst	31.72	18.66	21	24403	6068	79713896
Soft tissue neoplasm	31.64	18.66	7	24417	85	79719879
Haematocrit decreased	30.87	18.66	62	24362	61250	79658714
Metastases to bone marrow	30.80	18.66	11	24413	811	79719153
Trichorrhexis	30.79	18.66	11	24413	812	79719152
Poikilocytosis	30.63	18.66	9	24415	355	79719609
Seizure	30.33	18.66	10	24414	188824	79531140
Glomerular filtration rate decreased	30.17	18.66	36	24388	22666	79697298
Adjusted calcium decreased	30.11	18.66	8	24416	217	79719747
Pneumonitis	30.00	18.66	61	24363	60799	79659165
Creatinine renal clearance increased	29.68	18.66	11	24413	902	79719062
Monocyte count decreased	29.66	18.66	16	24408	3185	79716779
Osteolysis	29.64	18.66	18	24406	4480	79715484
Treatment failure	29.25	18.66	8	24416	170478	79549486
Product use issue	28.98	18.66	14	24410	209808	79510156
Nail avulsion	28.86	18.66	7	24417	130	79719834
Tumour marker decreased	28.65	18.66	6	24418	55	79719909
Neutrophil count abnormal	28.22	18.66	16	24408	3510	79716454
Metastases to peritoneum	27.55	18.66	17	24407	4355	79715609
Electrocardiogram QT interval abnormal	27.32	18.66	8	24416	312	79719652
Depressed mood	26.81	18.66	51	24373	48429	79671535
Mean cell volume increased	26.52	18.66	19	24405	6234	79713730
COVID-19	26.49	18.66	107	24317	157567	79562397
Hypermetabolism	26.00	18.66	8	24416	370	79719594
Breast pain	25.97	18.66	21	24403	8244	79711720
Metastases to skin	25.91	18.66	12	24412	1727	79718237
Asthma	25.84	18.66	5	24419	135090	79584874
Macrocytosis	25.64	18.66	14	24410	2856	79717108
BRCA2 gene mutation	25.58	18.66	6	24418	96	79719868
BRCA1 gene mutation	25.46	18.66	5	24419	32	79719932
Mean cell haemoglobin increased	25.33	18.66	16	24408	4269	79715695
Gastrointestinal haemorrhage	25.21	18.66	7	24417	147712	79572252
Selenium deficiency	25.20	18.66	5	24419	34	79719930
Taste disorder	24.23	18.66	27	24397	15796	79704168
Hepatobiliary disease	23.88	18.66	9	24415	773	79719191
Cardiac failure congestive	23.84	18.66	7	24417	142395	79577569
Metastases to spinal cord	23.39	18.66	5	24419	51	79719913
Vomiting	23.15	18.66	308	24116	665520	79054444
Invasive ductal breast carcinoma	22.94	18.66	17	24407	5875	79714089
Aphthous ulcer	22.80	18.66	27	24397	16862	79703102
General physical health deterioration	22.59	18.66	153	24271	275085	79444879
Lacrimation increased	22.54	18.66	31	24393	22446	79697518
Pleural thickening	22.44	18.66	13	24411	2969	79716995
Adjusted calcium increased	22.35	18.66	5	24419	64	79719900
Metastases to the mediastinum	22.24	18.66	8	24416	602	79719362
Confusional state	21.87	18.66	40	24384	317957	79402007
Metastases to uterus	21.74	18.66	5	24419	73	79719891
White blood cell disorder	21.62	18.66	13	24411	3179	79716785
Overdose	21.58	18.66	15	24409	184191	79535773
Electrocardiogram abnormal	21.35	18.66	26	24398	16711	79703253
Dorsal ramus syndrome	21.21	18.66	4	24420	20	79719944
Sinus arrhythmia	20.83	18.66	11	24413	2099	79717865
Hepatomegaly	20.41	18.66	27	24397	18847	79701117
Therapeutic product effect incomplete	20.25	18.66	9	24415	141636	79578328
Neoplasm	20.23	18.66	19	24405	9097	79710867
Blood lactate dehydrogenase increased	20.18	18.66	40	24384	39130	79680834
Swelling	20.12	18.66	22	24402	216689	79503275
Jaundice	20.09	18.66	48	24376	53301	79666663
Mucinous breast carcinoma	20.06	18.66	4	24420	28	79719936
Hypersensitivity	19.86	18.66	31	24393	262208	79457756
Depressed level of consciousness	19.75	18.66	3	24421	96649	79623315
Second primary malignancy	19.47	18.66	23	24401	14327	79705637
Metastases to breast	19.39	18.66	6	24418	283	79719681
Urticaria	19.27	18.66	17	24407	185184	79534780
Loss of consciousness	19.25	18.66	14	24410	167929	79552035
Calcium deficiency	19.23	18.66	8	24416	891	79719073
Erysipelas	19.23	18.66	20	24404	10830	79709134
Thrombasthenia	19.20	18.66	3	24421	3	79719961
Loss of personal independence in daily activities	19.19	18.66	4	24420	102576	79617388
Blood pressure increased	19.03	18.66	22	24402	211338	79508626
Osteosclerosis	19.02	18.66	13	24411	3958	79716006
Renal vein thrombosis	19.00	18.66	7	24417	564	79719400
Weight increased	18.97	18.66	35	24389	277351	79442613
Hypoaesthesia teeth	18.70	18.66	4	24420	41	79719923
Oestradiol abnormal	18.70	18.66	4	24420	41	79719923

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	L01EF02	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PROTEIN KINASE INHIBITORS Cyclin-dependent kinase (CDK) inhibitors
FDA MoA	N0000175082	Kinase Inhibitors
FDA EPC	N0000175605	Kinase Inhibitor
FDA MoA	N0000190114	Cytochrome P450 3A Inhibitors

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Hormone receptor positive malignant neoplasm of breast	indication	417181009

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	8.03	Basic
pKa2	6.09	Basic
pKa3	5.48	Basic
pKa4	0.57	Basic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
EQ 200MG BASE	KISQALI	NOVARTIS	N209092	March 13, 2017	RX	TABLET	ORAL	9416136	Aug. 20, 2029	IN COMBINATION WITH AN AROMATASE INHIBITOR AS INITIAL ENDOCRINE-BASED THERAPY FOR THE TREATMENT OF ADULT PATIENTS WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
EQ 200MG BASE	KISQALI	NOVARTIS	N209092	March 13, 2017	RX	TABLET	ORAL	9416136	Aug. 20, 2029	IN COMBINATION WITH AN AROMATASE INHIBITOR AS INITIAL ENDOCRINE-BASED THERAPY FOR TREATMENT OF POSTMENOPAUSAL WOMEN WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER-2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
EQ 200MG BASE	KISQALI	NOVARTIS	N209092	March 13, 2017	RX	TABLET	ORAL	9416136	Aug. 20, 2029	IN COMBINATION WITH AN AROMATASE INHIBITOR FOR THE TREATMENT OF PRE/PERIMENOPAUSAL OR POSTMENOPAUSAL WOMEN WITH HR-POSITIVE, HER2-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER, AS INITIAL ENDOCRINE-BASED THERAPY
EQ 200MG BASE	KISQALI	NOVARTIS	N209092	March 13, 2017	RX	TABLET	ORAL	9416136	Aug. 20, 2029	IN COMBINATION WITH FULVESTRANT AS INITIAL ENDOCRINE-BASED THERAPY OR FOLLOWING DISEASE PROGRESSION ON ENDOCRINE THERAPY IN POSTMENOPAUSAL WOMEN OR IN MEN, FOR THE TREATMENT OF HR-POSITIVE, HER2-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
EQ 200MG BASE	KISQALI	NOVARTIS	N209092	March 13, 2017	RX	TABLET	ORAL	9416136	Aug. 20, 2029	IN COMBINATION WITH FULVESTRANT FOR THE TREATMENT OF POSTMENOPAUSAL WOMEN WITH HR-POSITIVE, HER2-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER, AS INITIAL ENDOCRINE BASED THERAPY OR FOLLOWING DISEASE PROGRESSION ON ENDOCRINE THERAPY
2.5MG;EQ 200MG BASE	KISQALI FEMARA CO-PACK (COPACKAGED)	NOVARTIS	N209935	May 4, 2017	RX	TABLET	ORAL	9416136	Aug. 20, 2029	AS INITIAL ENDOCRINE-BASED THERAPY FOR THE TREATMENT OF ADULT PATIENTS WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
2.5MG;EQ 200MG BASE	KISQALI FEMARA CO-PACK (COPACKAGED)	NOVARTIS	N209935	May 4, 2017	RX	TABLET	ORAL	9416136	Aug. 20, 2029	TREATMENT OF PRE/PERIMENOPAUSAL WOMEN WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
EQ 200MG BASE	KISQALI	NOVARTIS	N209092	March 13, 2017	RX	TABLET	ORAL	8962630	Dec. 9, 2029	IN COMBINATION WITH AN AROMATASE INHIBITOR AS INITIAL ENDOCRINE-BASED THERAPY FOR THE TREATMENT OF ADULT PATIENTS WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
EQ 200MG BASE	KISQALI	NOVARTIS	N209092	March 13, 2017	RX	TABLET	ORAL	8962630	Dec. 9, 2029	IN COMBINATION WITH AN AROMATASE INHIBITOR AS INITIAL ENDOCRINE-BASED THERAPY FOR TREATMENT OF POSTMENOPAUSAL WOMEN WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER-2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
EQ 200MG BASE	KISQALI	NOVARTIS	N209092	March 13, 2017	RX	TABLET	ORAL	8962630	Dec. 9, 2029	IN COMBINATION WITH AN AROMATASE INHIBITOR FOR THE TREATMENT OF PRE/PERIMENOPAUSAL OR POSTMENOPAUSAL WOMEN WITH HR-POSITIVE, HER2-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER, AS INITIAL ENDOCRINE-BASED THERAPY
EQ 200MG BASE	KISQALI	NOVARTIS	N209092	March 13, 2017	RX	TABLET	ORAL	8962630	Dec. 9, 2029	IN COMBINATION WITH FULVESTRANT AS INITIAL ENDOCRINE-BASED THERAPY OR FOLLOWING DISEASE PROGRESSION ON ENDOCRINE THERAPY IN POSTMENOPAUSAL WOMEN OR IN MEN, FOR THE TREATMENT OF HR-POSITIVE, HER2-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
EQ 200MG BASE	KISQALI	NOVARTIS	N209092	March 13, 2017	RX	TABLET	ORAL	8962630	Dec. 9, 2029	IN COMBINATION WITH FULVESTRANT FOR THE TREATMENT OF POSTMENOPAUSAL WOMEN WITH HR-POSITIVE, HER2-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER, AS INITIAL ENDOCRINE BASED THERAPY OR FOLLOWING DISEASE PROGRESSION ON ENDOCRINE THERAPY
2.5MG;EQ 200MG BASE	KISQALI FEMARA CO-PACK (COPACKAGED)	NOVARTIS	N209935	May 4, 2017	RX	TABLET	ORAL	8962630	Dec. 9, 2029	AS INITIAL ENDOCRINE-BASED THERAPY FOR THE TREATMENT OF ADULT PATIENTS WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
2.5MG;EQ 200MG BASE	KISQALI FEMARA CO-PACK (COPACKAGED)	NOVARTIS	N209935	May 4, 2017	RX	TABLET	ORAL	8962630	Dec. 9, 2029	TREATMENT OF PRE/PERIMENOPAUSAL WOMEN WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
EQ 200MG BASE	KISQALI	NOVARTIS	N209092	March 13, 2017	RX	TABLET	ORAL	9868739	Nov. 9, 2031	IN COMBINATION WITH AN AROMATASE INHIBITOR AS INITIAL ENDOCRINE-BASED THERAPY FOR THE TREATMENT OF ADULT PATIENTS WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
EQ 200MG BASE	KISQALI	NOVARTIS	N209092	March 13, 2017	RX	TABLET	ORAL	9868739	Nov. 9, 2031	IN COMBINATION WITH AN AROMATASE INHIBITOR AS INITIAL ENDOCRINE-BASED THERAPY FOR TREATMENT OF POSTMENOPAUSAL WOMEN WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER-2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
EQ 200MG BASE	KISQALI	NOVARTIS	N209092	March 13, 2017	RX	TABLET	ORAL	9868739	Nov. 9, 2031	IN COMBINATION WITH AN AROMATASE INHIBITOR FOR THE TREATMENT OF PRE/PERIMENOPAUSAL OR POSTMENOPAUSAL WOMEN WITH HR-POSITIVE, HER2-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER, AS INITIAL ENDOCRINE-BASED THERAPY
EQ 200MG BASE	KISQALI	NOVARTIS	N209092	March 13, 2017	RX	TABLET	ORAL	9868739	Nov. 9, 2031	IN COMBINATION WITH FULVESTRANT AS INITIAL ENDOCRINE-BASED THERAPY OR FOLLOWING DISEASE PROGRESSION ON ENDOCRINE THERAPY IN POSTMENOPAUSAL WOMEN OR IN MEN, FOR THE TREATMENT OF HR-POSITIVE, HER2-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
EQ 200MG BASE	KISQALI	NOVARTIS	N209092	March 13, 2017	RX	TABLET	ORAL	9868739	Nov. 9, 2031	IN COMBINATION WITH FULVESTRANT FOR THE TREATMENT OF POSTMENOPAUSAL WOMEN WITH HR-POSITIVE, HER2-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER, AS INITIAL ENDOCRINE BASED THERAPY OR FOLLOWING DISEASE PROGRESSION ON ENDOCRINE THERAPY
2.5MG;EQ 200MG BASE	KISQALI FEMARA CO-PACK (COPACKAGED)	NOVARTIS	N209935	May 4, 2017	RX	TABLET	ORAL	9868739	Nov. 9, 2031	AS INITIAL ENDOCRINE-BASED THERAPY FOR THE TREATMENT OF ADULT PATIENTS WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
2.5MG;EQ 200MG BASE	KISQALI FEMARA CO-PACK (COPACKAGED)	NOVARTIS	N209935	May 4, 2017	RX	TABLET	ORAL	9868739	Nov. 9, 2031	TREATMENT OF PRE/PERIMENOPAUSAL WOMEN WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
EQ 200MG BASE	KISQALI	NOVARTIS	N209092	March 13, 2017	RX	TABLET	ORAL	Dec. 10, 2024	NEW PATIENT POPULATION
2.5MG;EQ 200MG BASE	KISQALI FEMARA CO-PACK (COPACKAGED)	NOVARTIS	N209935	May 4, 2017	RX	TABLET	ORAL	Dec. 10, 2024	NEW PATIENT POPULATION

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Cyclin-dependent kinase 6	Kinase	Q00534	CDK6_HUMAN	INHIBITOR	IC50	7.41	SCIENTIFIC LITERATURE	DRUG LABEL
Cyclin-dependent kinase 4	Kinase	P11802	CDK4_HUMAN	INHIBITOR	IC50	8	SCIENTIFIC LITERATURE	DRUG LABEL
Calcium/calmodulin-dependent protein kinase type II subunit gamma	Kinase	Q13555	KCC2G_HUMAN		Kd	6.61	CHEMBL
Cyclin-G-associated kinase	Kinase	O14976	GAK_HUMAN		Kd	6.18	CHEMBL
Cyclin-dependent kinase 16	Kinase	Q00536	CDK16_HUMAN		Kd	5.42	CHEMBL
Cyclin-dependent kinase 9	Kinase	P50750	CDK9_HUMAN		Kd	5.43	CHEMBL
Cyclin-dependent kinase 2	Kinase	P24941	CDK2_HUMAN		IC50	4.12	CHEMBL
Serine/threonine-protein kinase D2	Kinase	Q9BZL6	KPCD2_HUMAN		Kd	4.60	CHEMBL
Mitogen-activated protein kinase kinase kinase 1	Kinase	Q13233	M3K1_HUMAN		Kd	4.90	CHEMBL
Ferrochelatase, mitochondrial	Enzyme	P22830	HEMH_HUMAN		Kd	4.91	CHEMBL
Uncharacterized protein FLJ45252	Unclassified	Q6ZSR9	YJ005_HUMAN		Kd	5.03	CHEMBL
Serine/threonine-protein kinase SIK2	Kinase	Q9H0K1	SIK2_HUMAN		Kd	5.60	CHEMBL
Calcium/calmodulin-dependent protein kinase type II subunit delta	Kinase	Q13557	KCC2D_HUMAN		Kd	6.53	CHEMBL

External reference:

ID	Source
TK8ERE8P56	UNII
1374639-75-4	SECONDARY_CAS_RN
4036504	VANDF
C4045494	UMLSCUI
6ZZ	PDB_CHEM_ID
CHEMBL3545110	ChEMBL_ID
44631912	PUBCHEM_CID
DB11730	DRUGBANK_ID
CHEMBL3707266	ChEMBL_ID
D10883	KEGG_DRUG
9968	INN_ID
7383	IUPHAR_LIGAND_ID
254040	MMSL
32443	MMSL
d08533	MMSL
017131	NDDF
017132	NDDF
732257004	SNOMEDCT_US
732258009	SNOMEDCT_US
763537002	SNOMEDCT_US
1873916	RXNORM
C000589651	MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
KISQALI	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0860	TABLET, FILM COATED	200 mg	ORAL	NDA	33 sections
KISQALI	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0860	TABLET, FILM COATED	200 mg	ORAL	NDA	33 sections
KISQALI	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0860	TABLET, FILM COATED	200 mg	ORAL	NDA	33 sections
KISQALI	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0860	TABLET, FILM COATED	200 mg	ORAL	NDA	33 sections
KISQALI	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0867	TABLET, FILM COATED	200 mg	ORAL	NDA	33 sections
KISQALI	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0867	TABLET, FILM COATED	200 mg	ORAL	NDA	33 sections
KISQALI	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0867	TABLET, FILM COATED	200 mg	ORAL	NDA	33 sections
KISQALI	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0867	TABLET, FILM COATED	200 mg	ORAL	NDA	33 sections
KISQALI	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0874	TABLET, FILM COATED	200 mg	ORAL	NDA	33 sections
KISQALI	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0874	TABLET, FILM COATED	200 mg	ORAL	NDA	33 sections
KISQALI	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0874	TABLET, FILM COATED	200 mg	ORAL	NDA	33 sections
KISQALI	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0874	TABLET, FILM COATED	200 mg	ORAL	NDA	33 sections