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:

None

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	2334.22	20.12	1314	29207	146651	50427952
Leukopenia	1087.08	20.12	610	29911	66918	50507685
Malignant neoplasm progression	1084.79	20.12	611	29910	67513	50507090
Metastases to bone	678.20	20.12	291	30230	17704	50556899
Electrocardiogram QT prolonged	532.90	20.12	352	30169	51534	50523069
Metastases to liver	462.70	20.12	231	30290	19873	50554730
Hepatotoxicity	287.23	20.12	188	30333	27038	50547565
Aspartate aminotransferase increased	262.03	20.12	277	30244	77721	50496882
Alanine aminotransferase increased	257.21	20.12	291	30230	88068	50486535
Metastases to lung	251.60	20.12	126	30395	10894	50563709
Thrombocytopenia	249.08	20.12	344	30177	127329	50447274
General physical health deterioration	245.86	20.12	362	30159	142072	50432531
Drug ineffective	245.15	20.12	95	30426	819238	49755365
White blood cell count decreased	242.07	20.12	324	30197	116398	50458205
Gamma-glutamyltransferase increased	240.32	20.12	174	30347	29449	50545154
Skin hypopigmentation	239.01	20.12	59	30462	572	50574031
Neutrophil count decreased	225.18	20.12	201	30320	45825	50528778
Carbohydrate antigen 15-3 increased	218.29	20.12	62	30459	1070	50573533
Anaemia	192.46	20.12	451	30070	252005	50322598
Bone lesion	169.91	20.12	76	30445	5094	50569509
Bone pain	160.72	20.12	169	30352	47060	50527543
Polyneuropathy	158.57	20.12	96	30425	12035	50562568
Nausea	156.98	20.12	836	29685	704562	49870041
Pleural effusion	153.45	20.12	216	30305	81238	50493365
Off label use	148.09	20.12	51	30470	474375	50100228
Metastases to lymph nodes	141.98	20.12	74	30447	6950	50567653
Liver function test increased	135.54	20.12	117	30404	25489	50549114
Blood creatinine increased	133.23	20.12	195	30326	75965	50498638
Transaminases increased	123.28	20.12	115	30406	27709	50546894
Eastern Cooperative Oncology Group performance status worsened	123.27	20.12	35	30486	603	50574000
Hot flush	115.84	20.12	138	30383	44031	50530572
Tumour marker increased	112.15	20.12	52	30469	3788	50570815
Drug hypersensitivity	111.87	20.12	11	30510	250999	50323604
Breast cancer metastatic	105.42	20.12	70	30451	10294	50564309
PIK3CA-activated mutation	102.33	20.12	32	30489	778	50573825
Condition aggravated	99.57	20.12	28	30493	297030	50277573
Erysipelas	93.39	20.12	55	30466	6553	50568050
Fatigue	92.37	20.12	734	29787	706867	49867736
Arthropathy	82.00	20.12	3	30518	157903	50416700
Blood alkaline phosphatase increased	80.42	20.12	106	30415	37420	50537183
Blood bilirubin increased	70.98	20.12	92	30429	31946	50542657
Carcinoembryonic antigen increased	69.50	20.12	28	30493	1446	50573157
Metastases to pleura	69.23	20.12	27	30494	1279	50573324
Metastases to central nervous system	68.88	20.12	56	30465	11226	50563377
Lymphoedema	68.10	20.12	51	30470	9071	50565532
Ascites	65.83	20.12	94	30427	35767	50538836
Hypertensive crisis	65.36	20.12	58	30463	13096	50561507
Pyelitis	63.83	20.12	16	30505	166	50574437
Glomerular filtration rate decreased	63.18	20.12	54	30467	11598	50563005
Taste disorder	63.17	20.12	47	30474	8277	50566326
Bone marrow infiltration	61.27	20.12	19	30502	449	50574154
Joint swelling	61.27	20.12	36	30485	245250	50329353
Metastases to spine	60.59	20.12	31	30490	2800	50571803
Hypotension	59.60	20.12	34	30487	235435	50339168
Dry skin	59.31	20.12	99	30422	43092	50531511
Sinusitis	59.11	20.12	15	30506	170543	50404060
Metastasis	58.13	20.12	35	30486	4340	50570263
Lacrimation increased	58.10	20.12	61	30460	16931	50557672
Osteonecrosis of jaw	57.86	20.12	84	30437	32442	50542161
Hypocalcaemia	56.29	20.12	75	30446	26741	50547862
Treatment failure	54.11	20.12	9	30512	137628	50436975
Product use issue	54.05	20.12	12	30509	149463	50425140
Alopecia	53.61	20.12	290	30231	244757	50329846
Decreased appetite	53.23	20.12	251	30270	200672	50373931
Breast cancer recurrent	51.99	20.12	31	30490	3777	50570826
Calcium deficiency	51.63	20.12	20	30501	930	50573673
Blood lactate dehydrogenase increased	51.06	20.12	61	30460	19501	50555102
Electrocardiogram PR shortened	50.62	20.12	14	30507	218	50574385
Constipation	49.92	20.12	233	30288	185475	50389128
Spinal pain	48.50	20.12	45	30476	10758	50563845
Isosthenuria	45.39	20.12	11	30510	98	50574505
Haemoglobin decreased	45.36	20.12	174	30347	127042	50447561
Toxicity to various agents	45.33	20.12	37	30484	212462	50362141
Vitiligo	44.53	20.12	19	30502	1135	50573468
Urinary tract inflammation	44.10	20.12	9	30512	32	50574571
Swelling	44.07	20.12	34	30487	200838	50373765
Pneumonitis	42.34	20.12	69	30452	29441	50545162
Anisocytosis	41.70	20.12	15	30506	566	50574037
Musculoskeletal stiffness	41.35	20.12	13	30508	128468	50446135
Weight increased	40.81	20.12	37	30484	201854	50372749
Hepatic lesion	40.58	20.12	27	30494	3981	50570622
Tumour pain	40.15	20.12	18	30503	1212	50573391
Hypersensitivity	39.40	20.12	43	30478	215118	50359485
Wound	39.25	20.12	8	30513	105786	50468817
Elliptocytosis	38.66	20.12	8	30513	31	50574572
Decreased immune responsiveness	38.59	20.12	26	30495	3915	50570688
Metastases to peritoneum	38.51	20.12	23	30498	2810	50571793
Disease progression	38.25	20.12	136	30385	95730	50478873
Bladder hypertrophy	37.78	20.12	11	30510	208	50574395
Drug intolerance	37.73	20.12	46	30475	219058	50355545
Breast pain	36.95	20.12	33	30488	7511	50567092
Fall	36.29	20.12	94	30427	334838	50239765
Neutrophil count abnormal	36.15	20.12	21	30500	2438	50572165
Haematotoxicity	35.66	20.12	33	30488	7862	50566741
Hepatobiliary disease	34.96	20.12	11	30510	273	50574330
Cardiac failure congestive	34.33	20.12	5	30516	84377	50490226
Arthritis	33.35	20.12	6	30515	86715	50487888
Injection site pain	32.70	20.12	13	30508	111011	50463592
CYP3A4 polymorphism	32.18	20.12	8	30513	80	50574523
Lymphocyte count decreased	31.79	20.12	57	30464	26250	50548353
Hepatic failure	31.66	20.12	64	30457	32219	50542384
C-reactive protein increased	31.55	20.12	100	30421	66374	50508229
Loss of personal independence in daily activities	31.34	20.12	3	30518	70047	50504556
Seizure	31.28	20.12	16	30505	117858	50456745
Concomitant disease aggravated	31.21	20.12	31	30490	8060	50566543
Neoplasm	31.17	20.12	27	30494	5901	50568702
Loss of consciousness	31.09	20.12	12	30509	104341	50470262
Psoriasis	30.75	20.12	3	30518	68997	50505606
Dry eye	30.73	20.12	63	30458	32032	50542571
Asthma	30.66	20.12	8	30513	89329	50485274
Therapy partial responder	30.64	20.12	28	30493	6563	50568040
Abdominal discomfort	29.96	20.12	59	30462	231582	50343021
Discomfort	29.84	20.12	14	30507	108366	50466237
Urticaria	29.60	20.12	21	30500	129540	50445063
Sinus arrhythmia	29.32	20.12	15	30506	1354	50573249
Dyspnoea exertional	28.97	20.12	82	30439	51151	50523452
Sleep disorder	28.87	20.12	88	30433	57195	50517408
Adjusted calcium decreased	28.84	20.12	8	30513	126	50574477
Mucosal inflammation	28.57	20.12	70	30451	40072	50534531
Hypermetabolism	27.39	20.12	8	30513	153	50574450
Skin toxicity	27.27	20.12	21	30500	3892	50570711
Radiation oesophagitis	27.21	20.12	9	30512	263	50574340
Intentional overdose	27.12	20.12	3	30518	62501	50512102
Hyperchromic anaemia	26.69	20.12	6	30515	37	50574566
Product dose omission issue	26.28	20.12	44	30477	183794	50390809
Blood phosphorus decreased	25.68	20.12	20	30501	3769	50570834
Jaundice	25.45	20.12	52	30469	26377	50548226
Red blood cell count decreased	25.14	20.12	60	30461	33775	50540828
Adjusted calcium increased	24.91	20.12	5	30516	16	50574587
Hydrothorax	24.83	20.12	11	30510	720	50573883
COVID-19	24.76	20.12	73	30448	46589	50528014
Overdose	24.35	20.12	15	30506	99712	50474891
Tumour marker decreased	24.32	20.12	6	30515	58	50574545
Malaise	24.24	20.12	112	30409	335420	50239183
Creatinine renal clearance increased	23.91	20.12	10	30511	568	50574035
Invasive breast carcinoma	23.80	20.12	10	30511	575	50574028
Lower respiratory tract infection	23.69	20.12	14	30507	95187	50479416
Metastases to skin	23.54	20.12	13	30508	1370	50573233
Lymphadenopathy	23.39	20.12	58	30463	33441	50541162
Electrocardiogram QT interval abnormal	23.13	20.12	7	30514	152	50574451
Osteolysis	22.98	20.12	16	30505	2541	50572062
Gastrointestinal haemorrhage	22.57	20.12	8	30513	73313	50501290
Oxygen saturation decreased	22.53	20.12	8	30513	73240	50501363
Wheezing	22.38	20.12	5	30516	62042	50512561
Monocyte count decreased	22.28	20.12	14	30507	1872	50572731
Skin reaction	22.22	20.12	31	30490	11537	50563066
Malignant pleural effusion	21.93	20.12	15	30506	2315	50572288
Migraine	21.86	20.12	9	30512	75271	50499332
Haematocrit decreased	21.78	20.12	58	30463	34918	50539685
Back pain	21.56	20.12	215	30306	219815	50354788
Aspartate aminotransferase abnormal	21.38	20.12	11	30510	1005	50573598
Pleural disorder	21.07	20.12	9	30512	539	50574064
Irritable bowel syndrome	21.03	20.12	3	30518	51438	50523165
Oedema peripheral	20.97	20.12	165	30356	157796	50416807
Suicidal ideation	20.93	20.12	4	30517	55381	50519222
Bone sequestrum	20.87	20.12	12	30509	1366	50573237
Blood cholesterol increased	20.84	20.12	4	30517	55211	50519392
Metastases to thorax	20.77	20.12	7	30514	217	50574386
Poikilocytosis	20.73	20.12	6	30515	111	50574492
Pruritus	20.49	20.12	261	30260	283307	50291296
Second primary malignancy	20.45	20.12	23	30498	6891	50567712
Hyperbilirubinaemia	20.44	20.12	27	30494	9543	50565060
Basophil count increased	20.43	20.12	10	30511	822	50573781
Trichorrhexis	20.28	20.12	11	30510	1119	50573484
Onychoclasis	20.21	20.12	20	30501	5176	50569427
Mean cell haemoglobin increased	20.20	20.12	14	30507	2206	50572397

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	1039.52	19.75	686	15932	238938	64243176
Metastases to bone	541.16	19.75	202	16416	20233	64461881
Malignant neoplasm progression	508.30	19.75	332	16286	112539	64369575
Metastases to liver	329.09	19.75	148	16470	23793	64458321
Electrocardiogram QT prolonged	316.97	19.75	217	16401	79231	64402883
Skin hypopigmentation	264.50	19.75	58	16560	813	64481301
Bone lesion	209.24	19.75	70	16548	5067	64477047
Carbohydrate antigen 15-3 increased	193.42	19.75	46	16572	941	64481173
Metastases to lung	192.77	19.75	89	16529	15175	64466939
Leukopenia	169.74	19.75	167	16451	101075	64381039
Hepatotoxicity	168.32	19.75	113	16505	39849	64442265
White blood cell count decreased	145.80	19.75	191	16427	157646	64324468
Neutrophil count decreased	128.69	19.75	127	16491	77069	64405045
Metastases to lymph nodes	126.44	19.75	56	16562	8661	64473453
Tumour marker increased	105.63	19.75	38	16580	3412	64478702
Alanine aminotransferase increased	105.38	19.75	153	16465	138878	64343236
Breast cancer metastatic	103.80	19.75	46	16572	7123	64474991
Nausea	95.65	19.75	427	16191	785373	63696741
Aspartate aminotransferase increased	93.93	19.75	134	16484	119654	64362460
Bone pain	86.26	19.75	82	16536	47490	64434624
Gamma-glutamyltransferase increased	77.45	19.75	78	16540	48432	64433682
Thrombocytopenia	71.85	19.75	170	16448	223631	64258483
Drug ineffective	69.25	19.75	69	16549	840178	63641936
Off label use	68.72	19.75	39	16579	632767	63849347
PIK3CA-activated mutation	65.32	19.75	17	16601	508	64481606
Breast cancer recurrent	62.73	19.75	24	16594	2559	64479555
Carcinoembryonic antigen increased	62.53	19.75	22	16596	1851	64480263
Anaemia	61.06	19.75	225	16393	378455	64103659
Electrocardiogram PR shortened	60.24	19.75	14	16604	258	64481856
Liver function test increased	59.22	19.75	55	16563	30915	64451199
Pleural effusion	56.54	19.75	110	16508	126449	64355665
Transaminases increased	55.78	19.75	63	16555	44531	64437583
Blood creatinine increased	54.66	19.75	113	16505	135669	64346445
Isosthenuria	54.41	19.75	11	16607	101	64482013
Condition aggravated	49.72	19.75	17	16601	372409	64109705
Anisocytosis	48.40	19.75	15	16603	848	64481266
Metastasis	47.37	19.75	25	16593	5670	64476444
Decreased immune responsiveness	47.14	19.75	23	16595	4425	64477689
Urinary tract inflammation	45.74	19.75	9	16609	71	64482043
Elliptocytosis	45.45	19.75	8	16610	31	64482083
Metastases to spine	45.22	19.75	21	16597	3622	64478492
Hypotension	44.95	19.75	21	16597	380953	64101161
Pyelitis	44.03	19.75	11	16607	278	64481836
Fatigue	42.86	19.75	334	16284	748396	63733718
Metastases to pleura	42.78	19.75	15	16603	1249	64480865
Metastases to central nervous system	41.66	19.75	32	16586	13880	64468234
Haemoglobin decreased	40.24	19.75	126	16492	194937	64287177
Blood alkaline phosphatase increased	39.77	19.75	60	16558	56219	64425895
Hot flush	39.58	19.75	54	16564	46181	64435933
Blood bilirubin increased	38.76	19.75	60	16558	57493	64424621
Hepatic lesion	38.59	19.75	22	16596	5802	64476312
Vitiligo	37.88	19.75	15	16603	1753	64480361
Bladder hypertrophy	36.74	19.75	11	16607	553	64481561
Alopecia	36.00	19.75	109	16509	165581	64316533
Fall	35.62	19.75	33	16585	416793	64065321
Pruritus	35.60	19.75	167	16451	312233	64169881
Eastern Cooperative Oncology Group performance status worsened	35.42	19.75	13	16605	1235	64480879
Trichorrhexis	34.10	19.75	11	16607	709	64481405
CYP3A4 polymorphism	34.08	19.75	7	16611	70	64482044
Adjusted calcium decreased	33.99	19.75	8	16610	156	64481958
Neutrophil count abnormal	33.80	19.75	16	16602	2880	64479234
Blood phosphorus decreased	33.69	19.75	20	16598	5685	64476429
Lymphadenopathy	33.31	19.75	50	16568	46636	64435478
Drug hypersensitivity	33.22	19.75	10	16608	237805	64244309
Haematotoxicity	32.91	19.75	27	16591	12869	64469245
General physical health deterioration	32.45	19.75	121	16497	204304	64277810
Therapy partial responder	31.63	19.75	24	16594	10224	64471890
Tumour marker decreased	30.64	19.75	6	16612	46	64482068
Back pain	30.16	19.75	136	16482	250035	64232079
Lymphocyte count decreased	29.62	19.75	44	16574	40655	64441459
Hypermetabolism	28.86	19.75	8	16610	305	64481809
Dry skin	28.56	19.75	49	16569	51112	64431002
Creatinine renal clearance increased	28.37	19.75	10	16608	846	64481268
Metastases to peritoneum	27.89	19.75	15	16603	3532	64478582
BRCA1 gene mutation	27.54	19.75	5	16613	24	64482090
Glomerular filtration rate decreased	26.79	19.75	29	16589	19543	64462571
Red blood cell count decreased	26.56	19.75	46	16572	48340	64433774
Nail avulsion	26.38	19.75	6	16612	100	64482014
Hypocalcaemia	25.99	19.75	42	16576	41711	64440403
Toxicity to various agents	25.31	19.75	34	16584	363479	64118635
Osteolysis	25.30	19.75	13	16605	2790	64479324
Disease progression	25.14	19.75	87	16531	141593	64340521
Metastases to the mediastinum	24.64	19.75	8	16610	526	64481588
Taste disorder	24.59	19.75	20	16598	9413	64472701
Adjusted calcium increased	24.17	19.75	5	16613	52	64482062
Blood calcium increased	24.17	19.75	19	16599	8523	64473591
Metastases to uterus	23.75	19.75	5	16613	57	64482057
Spinal pain	23.32	19.75	22	16596	12599	64469515
Hepatobiliary disease	23.05	19.75	8	16610	646	64481468
Breast pain	22.82	19.75	17	16601	7044	64475070
Haematocrit decreased	22.57	19.75	46	16572	54609	64427505
Depressed mood	22.52	19.75	39	16579	40973	64441141
Joint swelling	22.26	19.75	14	16604	215368	64266746
Pleural disorder	22.17	19.75	8	16610	724	64481390
Calcium deficiency	22.11	19.75	8	16610	730	64481384
Rouleaux formation	21.79	19.75	3	16615	0	64482114
Vomiting	21.71	19.75	227	16391	550890	63931224
Hydrothorax	21.25	19.75	9	16609	1248	64480866
Cardiac failure congestive	21.15	19.75	4	16614	130576	64351538
Metastases to ovary	20.99	19.75	6	16612	256	64481858
Mean cell haemoglobin increased	20.96	19.75	12	16606	3190	64478924
Sinus arrhythmia	20.81	19.75	10	16608	1860	64480254
Psychomotor disadaptation syndrome	20.62	19.75	4	16614	29	64482085
Sinusitis	20.62	19.75	6	16612	145922	64336192
Breast cancer	20.48	19.75	31	16587	29117	64452997
Poikilocytosis	20.41	19.75	6	16612	283	64481831
Constipation	20.10	19.75	114	16504	229223	64252891
Pleural thickening	20.03	19.75	11	16607	2699	64479415
Breast mass	19.93	19.75	14	16604	5296	64476818

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	March 13, 2022	NEW CHEMICAL ENTITY
2.5MG;EQ 200MG BASE	KISQALI FEMARA CO-PACK (COPACKAGED)	NOVARTIS	N209935	May 4, 2017	RX	TABLET	ORAL	March 13, 2022	NEW CHEMICAL ENTITY
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
C4045494	UMLSCUI
6ZZ	PDB_CHEM_ID
CHEMBL3545110	ChEMBL_ID
44631912	PUBCHEM_CID
DB11730	DRUGBANK_ID
CHEMBL3707266	ChEMBL_ID
D10883	KEGG_DRUG
7383	IUPHAR_LIGAND_ID
1873916	RXNORM
254040	MMSL
32443	MMSL
d08533	MMSL
732257004	SNOMEDCT_US
732258009	SNOMEDCT_US
763537002	SNOMEDCT_US
4036504	VANDF
017131	NDDF
017132	NDDF
C000589651	MESH_SUPPLEMENTAL_RECORD_UI
9968	INN_ID
1374639-75-4	SECONDARY_CAS_RN

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	0078-0867	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