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

Stem definitionDrug idCAS RN
cyclin dependant kinase inhibitors 5218 1211441-98-3

Description:

MoleculeDescription

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:

DoseUnitRoute
0.45 g O

ADMET properties:

PropertyValueReference
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:

DateAgencyCompanyOrphan
Aug. 22, 2017 EMA Novartis Europharm Ltd
March 13, 2017 FDA NOVARTIS PHARMS CORP

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients 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 termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients 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:

SourceCodeDescription
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|

DiseaseRelationSNOMED_IDDOID
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 levelDissociation constantType (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 strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent 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 strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
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:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Cyclin-dependent kinase 6 Kinase INHIBITOR IC50 7.41 SCIENTIFIC LITERATURE DRUG LABEL
Cyclin-dependent kinase 4 Kinase INHIBITOR IC50 8 SCIENTIFIC LITERATURE DRUG LABEL
Calcium/calmodulin-dependent protein kinase type II subunit gamma Kinase Kd 6.61 CHEMBL
Cyclin-G-associated kinase Kinase Kd 6.18 CHEMBL
Cyclin-dependent kinase 16 Kinase Kd 5.42 CHEMBL
Cyclin-dependent kinase 9 Kinase Kd 5.43 CHEMBL
Cyclin-dependent kinase 2 Kinase IC50 4.12 CHEMBL
Serine/threonine-protein kinase D2 Kinase Kd 4.60 CHEMBL
Mitogen-activated protein kinase kinase kinase 1 Kinase Kd 4.90 CHEMBL
Ferrochelatase, mitochondrial Enzyme Kd 4.91 CHEMBL
Uncharacterized protein FLJ45252 Unclassified Kd 5.03 CHEMBL
Serine/threonine-protein kinase SIK2 Kinase Kd 5.60 CHEMBL
Calcium/calmodulin-dependent protein kinase type II subunit delta Kinase Kd 6.53 CHEMBL

External reference:

IDSource
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:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
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