regorafenib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
Raf (Rapidely Accelerated Fibrosarcoma) kinase inhibitors 4654 755037-03-7

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • regorafenib monohydrate
  • Stivarga
  • regorafenib
  • regorafenib hydrate
  • anhydrous regorafenib
  • BAY 73-4506
Regorafenib is a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis, metastasis and tumor immunity. In in vitro biochemical or cellular assays, regorafenib or its major human active metabolites M-2 and M-5 inhibited the activity of RET, VEGFR1, VEGFR2, VEGFR3, KIT, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2, TIE2, DDR2, TrkA, Eph2A, RAF-1, BRAF, BRAF V600E, SAPK2, PTK5, Abl and CSF1R at concentrations of regorafenib that have been achieved clinically. In in vivo models, regorafenib demonstrated anti-angiogenic activity in a rat tumor model and inhibition of tumor growth in several mouse xenograft models including some for human colorectal carcinoma, gastrointestinal stromal and hepatocellular carcinoma. Regorafenib also demonstrated anti-metastatic activity in a mouse xenograft model and two mouse orthotopic models of human colorectal carcinoma.
  • Molecular weight: 482.82
  • Formula: C21H15ClF4N4O3
  • CLOGP: 4.88
  • LIPINSKI: 1
  • HAC: 7
  • HDO: 3
  • TPSA: 92.35
  • ALOGS: -5.67
  • ROTB: 6
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.12 g O

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 4.989 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 1.570 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 4.943 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 3.532 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 0.100 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 0.210 % High 1
herg hERG pIC50 4.862 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 6.095 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 4.018 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 0.220 % High 1
kinase-safety-class ABL1,ABL2,ACVR2A,ACVR2B,ACVRL1,AKT3,ALK,AURKA,AURKB,AURKC,AXL,BLK,BMX,BRAF,CAMK2B,CAMK2D,CDK1,CDK16,CDK19,CDK5,CDK9,CHEK1,CSF1R,CSK,DDR1,EGFR,EIF2AK3,EPHA2,EPHB1,EPHB3,EPHB4,ERBB2,ERBB4,FGFR1,FLT1,FLT3,FLT4,FYN,GAK,GRK2,IKBKB,INSR,IRAK1,ITK,JAK1,JAK2,KDR,KIT,LCK,LYN,MAP2K1,MAP2K6,MAP3K1,MAP3K10,MAP3K11,MAP3K21,MAP3K7,MAP4K1,MAP4K2,MAP4K3,MAP4K5,MAPK10,MAPK11,MAPK12,MAPK14,MAPK7,MAPK9,MAPKAPK2,MARK4,MELK,MET,MINK1,MST1R,MTOR,NTRK1,NTRK2,NTRK3,PAK4,PDGFRB,PDK1,PDK2,PDK4,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PRKCD,PRKDC,PTK6,RET,RIPK3,SIK2,SIK3,SRC,STK10,STK33,SYK,TEK,TNIK,TTK,TYRO3,ULK1,YES1 103
kinase-selectivity-class ABL2,ACVR2B,ALK,AURKA,AURKC,AXL,BLK,BMX,BRAF,CSF1R,CSK,DDR1,EGFR,EIF2AK3,EPHA2,EPHB4,ERBB2,FGFR1,FLT1,FLT3,FLT4,FYN,JAK1,KDR,KIT,LCK,LYN,MAP2K1,MAP2K6,MAP3K21,MAP4K1,MAP4K3,MAPK14,MET,MINK1,MKNK2,MST1R,NTRK3,PDGFRB,PDK4,PRKCD,RET,RIPK3,SIK2,SRC,STK10,STK33,SYK,TNIK,TYRO3,YES1 51
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 2.851 High 1
mh-clint Mouse hepatocyte intrinsic clearance 18.707 High 1
mppb Mouse plasma protein binding (% unbound) 0.120 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 2.904 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 1
pld-class Phospholipidosis risk class (1 = positive, 0 = negative) 1 High 0.83
pppb Pig plasma protein binding (% unbound) 0.320 % High 1
rat-kpuu-brain Rat brain Kpuu 0.555 % High 0.83
rh-clint Rat hepatocyte intrinsic clearance 5.610 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 0.520 % High 1
rppb Rat plasma protein binding (% unbound) 0.130 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 0.269 uM High 1

Approvals:

DateAgencyCompanyOrphan
Aug. 26, 2013 EMA
Sept. 27, 2012 FDA BAYER HLTHCARE

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
Palmar-plantar erythrodysaesthesia syndrome 1401.57 26.70 391 12845 27632 90587579
Dysphonia 432.33 26.70 202 13034 62882 90552329
Decreased appetite 237.60 26.70 283 12953 376257 90238954
Off label use 230.92 26.70 499 12737 1101753 89513458
Metastases to lung 194.71 26.70 77 13159 15914 90599297
Fatigue 179.88 26.70 466 12770 1153557 89461654
Diarrhoea 131.39 26.70 365 12871 938825 89676386
Metastases to liver 125.59 26.70 68 13168 28739 90586472
Blood bilirubin increased 121.70 26.70 77 13159 43393 90571818
Hyperkeratosis 119.31 26.70 43 13193 6885 90608326
Pyrexia 116.13 26.70 280 12956 660205 89955006
Platelet count decreased 115.37 26.70 120 13116 136849 90478362
Neuropathy peripheral 113.58 26.70 119 13117 136851 90478360
Carcinoembryonic antigen increased 113.51 26.70 32 13204 2318 90612893
Asthenia 112.27 26.70 243 12993 533508 90081703
Skin exfoliation 107.73 26.70 85 13151 67828 90547383
Pain in extremity 103.84 26.70 213 13023 450316 90164895
Dehydration 101.17 26.70 133 13103 194314 90420897
Oral pain 94.24 26.70 59 13177 32624 90582587
Blood pressure increased 74.69 26.70 116 13120 197101 90418110
Hypertension 72.81 26.70 187 13049 457345 90157866
Hepatic function abnormal 69.25 26.70 56 13180 46232 90568979
Weight decreased 65.35 26.70 160 13076 379750 90235461
Condition aggravated 65.18 26.70 6 13230 595539 90019672
Rash 63.07 26.70 256 12980 795844 89819367
Disseminated intravascular coagulation 62.38 26.70 39 13197 21499 90593712
Jaundice 58.76 26.70 44 13192 32473 90582738
Colon cancer 56.68 26.70 29 13207 10915 90604296
Blister 55.57 26.70 118 13118 254880 90360331
Colon cancer metastatic 53.74 26.70 16 13220 1405 90613806
Skin toxicity 53.52 26.70 24 13212 6755 90608456
Erythema 53.36 26.70 109 13127 229137 90386074
Dry skin 53.27 26.70 65 13171 88008 90527203
Mucosal inflammation 53.02 26.70 53 13183 57572 90557639
Tumour marker increased 50.49 26.70 22 13214 5785 90609426
Infusion related reaction 48.97 26.70 3 13233 416777 90198434
Myelosuppression 46.94 26.70 48 13188 53543 90561668
Death 45.31 26.70 158 13078 456393 90158818
Abdominal pain 44.62 26.70 143 13093 395578 90219633
Ascites 44.08 26.70 44 13192 47696 90567515
Hospitalisation 43.85 26.70 72 13164 128028 90487183
Aspartate aminotransferase increased 43.83 26.70 64 13172 102873 90512338
Joint swelling 43.71 26.70 10 13226 503290 90111921
Colorectal cancer metastatic 43.00 26.70 12 13224 837 90614374
Hepatic encephalopathy 42.58 26.70 26 13210 13746 90601465
Plantar erythema 41.88 26.70 9 13227 208 90615003
Hepatic failure 41.15 26.70 39 13197 39689 90575522
Nasopharyngitis 39.80 26.70 6 13230 407098 90208113
Stomatitis 39.25 26.70 108 13128 274590 90340621
Exercise tolerance decreased 39.07 26.70 20 13216 7531 90607680
Skin fissures 35.04 26.70 27 13209 20782 90594429
Pain of skin 34.15 26.70 24 13212 16058 90599153
Constipation 34.03 26.70 104 13132 280291 90334920
Drug hypersensitivity 33.37 26.70 13 13223 463596 90151615
Wound 33.24 26.70 3 13233 302977 90312234
Intestinal obstruction 32.05 26.70 33 13203 37098 90578113
Feeding disorder 30.09 26.70 23 13213 17489 90597722
Weight increased 29.61 26.70 12 13224 417915 90197296
Rash maculo-papular 29.38 26.70 33 13203 40900 90574311
Disease progression 29.04 26.70 68 13168 156547 90458664
Proteinuria 28.29 26.70 25 13211 23266 90591945
Drug ineffective 28.08 26.70 106 13130 1384192 89231019
Metastases to peritoneum 27.45 26.70 13 13223 4142 90611069

FDA Adverse Event Reporting System (Male)

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
Palmar-plantar erythrodysaesthesia syndrome 2108.33 22.91 632 17040 19950 42583713
Dysphonia 688.22 22.91 301 17371 28149 42575514
Metastases to lung 394.53 22.91 156 17516 11268 42592395
Decreased appetite 346.09 22.91 412 17260 192725 42410938
Fatigue 285.42 22.91 583 17089 435058 42168605
Off label use 258.00 22.91 707 16965 637628 41966035
Metastases to liver 252.52 22.91 127 17545 16199 42587464
Diarrhoea 225.19 22.91 549 17123 460300 42143363
Blister 215.50 22.91 137 17535 27353 42576310
Hypertension 168.94 22.91 271 17401 166933 42436730
Carcinoembryonic antigen increased 147.49 22.91 40 17632 858 42602805
Blood bilirubin increased 134.55 22.91 123 17549 42129 42561534
Asthenia 127.35 22.91 326 17346 280467 42323196
Alpha 1 foetoprotein increased 126.32 22.91 34 17638 708 42602955
Pain in extremity 125.32 22.91 224 17448 150380 42453283
Skin exfoliation 105.87 22.91 107 17565 41446 42562217
Neuropathy peripheral 97.09 22.91 161 17511 101692 42501971
Weight decreased 87.48 22.91 235 17437 207713 42395950
Stomatitis 87.35 22.91 106 17566 50223 42553440
Hyperkeratosis 84.03 22.91 40 17632 4518 42599145
Ascites 78.89 22.91 107 17565 56571 42547092
Tumour marker increased 77.84 22.91 24 17648 820 42602843
Skin fissures 77.69 22.91 49 17623 9627 42594036
Hepatic function abnormal 75.82 22.91 100 17572 51467 42552196
Blood pressure increased 70.22 22.91 140 17532 101788 42501875
Dry skin 66.87 22.91 91 17581 48247 42555416
Metastases to lymph nodes 65.42 22.91 37 17635 5961 42597702
Colorectal cancer metastatic 62.67 22.91 21 17651 940 42602723
Hepatic encephalopathy 62.57 22.91 53 17619 16389 42587274
Dehydration 58.29 22.91 159 17513 141608 42462055
Oral pain 55.04 22.91 44 17628 12552 42591111
Febrile neutropenia 53.35 22.91 7 17665 185696 42417967
Abdominal pain upper 52.76 22.91 110 17562 82499 42521164
Myelosuppression 52.69 22.91 74 17598 40387 42563276
Gastrointestinal stromal tumour 51.70 22.91 19 17653 1119 42602544
Abdominal pain 49.23 22.91 182 17490 190289 42413374
Hospitalisation 48.66 22.91 100 17572 74230 42529433
Aphonia 46.11 22.91 26 17646 4163 42599500
Drug interaction 45.81 22.91 27 17645 266972 42336691
Condition aggravated 45.26 22.91 26 17646 260728 42342935
Glossodynia 43.63 22.91 25 17647 4127 42599536
Colon cancer 42.68 22.91 34 17638 9647 42594016
Metastases to peritoneum 40.63 22.91 20 17652 2429 42601234
Acute kidney injury 39.54 22.91 57 17615 367280 42236383
Product prescribing issue 39.22 22.91 28 17644 6745 42596918
Jaundice 38.85 22.91 59 17613 34530 42569133
Colon cancer metastatic 37.71 22.91 17 17655 1695 42601968
Proteinuria 37.57 22.91 47 17625 22936 42580727
COVID-19 36.81 22.91 3 17669 115945 42487718
Hepatic failure 35.92 22.91 60 17612 38040 42565623
Death 35.74 22.91 324 17348 470861 42132802
Drug ineffective 34.99 22.91 139 17533 630058 41973605
Malaise 34.95 22.91 177 17495 211979 42391684
Gait inability 34.65 22.91 45 17627 22788 42580875
Metastasis 33.26 22.91 22 17650 4683 42598980
Protein induced by vitamin K absence or antagonist II increased 33.24 22.91 7 17665 47 42603616
Toxicity to various agents 32.93 22.91 28 17644 229108 42374555
Metastases to adrenals 30.99 22.91 13 17659 1089 42602574
Pain of skin 30.64 22.91 26 17646 8054 42595609
Biliary obstruction 30.12 22.91 18 17654 3211 42600452
Gastrointestinal perforation 29.37 22.91 20 17652 4466 42599197
Cardiac arrest 29.35 22.91 5 17667 109315 42494348
General physical health deterioration 29.09 22.91 132 17540 151114 42452549
Angular cheilitis 28.22 22.91 8 17664 203 42603460
Overdose 27.85 22.91 5 17667 105259 42498404
Constipation 27.83 22.91 137 17535 162154 42441509
Hypotension 27.66 22.91 40 17632 257591 42346072
Metastases to bone 26.99 22.91 32 17640 14777 42588886
Metastases to central nervous system 26.95 22.91 27 17645 10328 42593335
Ammonia increased 26.37 22.91 19 17653 4640 42599023
Plantar erythema 25.53 22.91 6 17666 70 42603593
Dry mouth 25.31 22.91 53 17619 39826 42563837
Nephrotic syndrome 25.06 22.91 24 17648 8694 42594969
Neutropenia 24.45 22.91 28 17644 199403 42404260
Rectal cancer 24.35 22.91 14 17658 2326 42601337
Gait disturbance 23.89 22.91 92 17580 97908 42505755
Tumour rupture 23.81 22.91 8 17664 361 42603302
Hepatic pain 23.41 22.91 12 17660 1588 42602075

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
Palmar-plantar erythrodysaesthesia syndrome 3232.34 22.02 930 28398 40095 110519876
Dysphonia 1021.56 22.02 466 28862 75463 110484508
Metastases to lung 596.71 22.02 226 29102 22837 110537134
Decreased appetite 529.88 22.02 640 28688 475206 110084765
Off label use 441.92 22.02 1116 28212 1499069 109060902
Fatigue 388.24 22.02 934 28394 1215024 109344947
Metastases to liver 355.68 22.02 178 29150 35208 110524763
Diarrhoea 342.78 22.02 856 28472 1138649 109421322
Blood bilirubin increased 250.26 22.02 187 29141 75785 110484186
Asthenia 245.60 22.02 554 28774 688445 109871526
Neuropathy peripheral 240.37 22.02 266 29062 179011 110380960
Carcinoembryonic antigen increased 212.62 22.02 62 29266 2762 110557209
Skin exfoliation 205.97 22.02 177 29151 87474 110472497
Pain in extremity 197.56 22.02 413 28915 486705 110073266
Hypertension 181.20 22.02 410 28918 509674 110050297
Hyperkeratosis 163.85 22.02 69 29259 9170 110550801
Dehydration 155.10 22.02 271 29057 279240 110280731
Blister 149.60 22.02 238 29090 227138 110332833
Hepatic function abnormal 149.00 22.02 149 29179 89146 110470825
Weight decreased 147.34 22.02 359 28969 467698 110092273
Alpha 1 foetoprotein increased 146.30 22.02 36 29292 828 110559143
Oral pain 136.42 22.02 98 29230 37346 110522625
Blood pressure increased 132.39 22.02 242 29086 258131 110301840
Platelet count decreased 124.63 22.02 221 29107 230222 110329749
Ascites 116.20 22.02 133 29195 92675 110467296
Skin fissures 115.15 22.02 75 29253 24383 110535588
Dry skin 114.57 22.02 142 29186 107511 110452460
Pyrexia 107.13 22.02 496 28832 897769 109662202
Colon cancer 107.00 22.02 62 29266 16381 110543590
Condition aggravated 105.52 22.02 32 29296 734804 109825167
Myelosuppression 101.28 22.02 125 29203 94215 110465756
Death 95.40 22.02 402 28926 698467 109861504
Tumour marker increased 93.78 22.02 39 29289 5021 110554950
Colon cancer metastatic 88.86 22.02 31 29297 2470 110557501
Jaundice 88.20 22.02 93 29235 59143 110500828
Colorectal cancer metastatic 85.75 22.02 27 29301 1562 110558409
Stomatitis 82.42 22.02 205 29123 270037 110289934
Abdominal pain 81.05 22.02 309 29019 512680 110047291
Hepatic encephalopathy 80.82 22.02 64 29264 28192 110531779
Hospitalisation 77.41 22.02 137 29191 142356 110417615
Proteinuria 70.84 22.02 69 29259 39949 110520022
Mucosal inflammation 70.65 22.02 106 29222 96035 110463936
Infusion related reaction 70.46 22.02 9 29319 381153 110178818
Hepatic failure 70.43 22.02 89 29239 68650 110491321
Product prescribing issue 67.16 22.02 42 29286 12730 110547241
Metastases to peritoneum 64.64 22.02 31 29297 5579 110554392
Metastases to lymph nodes 63.28 22.02 43 29285 14989 110544982
Aspartate aminotransferase increased 61.56 22.02 133 29195 159803 110400168
Pain of skin 60.81 22.02 47 29281 19982 110539989
Weight increased 58.85 22.02 19 29309 419625 110140346
Arthropathy 57.71 22.02 5 29323 287517 110272454
Disease progression 57.16 22.02 168 29160 243866 110316105
Joint swelling 57.09 22.02 23 29305 442822 110117149
Drug hypersensitivity 56.28 22.02 25 29303 454065 110105906
Sinusitis 54.83 22.02 7 29321 296681 110263290
Disseminated intravascular coagulation 54.77 22.02 61 29267 41225 110518746
Constipation 54.36 22.02 213 29115 357573 110202398
Rash 53.82 22.02 387 28941 820577 109739394
Plantar erythema 52.91 22.02 13 29315 297 110559674
Drug ineffective 52.38 22.02 217 29111 1520323 109039648
Gastrointestinal stromal tumour 51.90 22.02 20 29308 2111 110557860
Erythema 51.35 22.02 182 29146 291265 110268706
Gastrointestinal perforation 50.87 22.02 29 29299 7427 110552544
Nasopharyngitis 49.99 22.02 21 29307 394340 110165631
Drug interaction 49.86 22.02 36 29292 500147 110059824
Asthma 48.51 22.02 5 29323 250286 110309685
Exercise tolerance decreased 47.22 22.02 33 29295 12034 110547937
Metastasis 45.53 22.02 28 29300 8239 110551732
Wheezing 44.87 22.02 7 29321 255223 110304748
COVID-19 44.75 22.02 6 29322 245054 110314917
Skin toxicity 43.27 22.02 31 29297 11752 110548219
Metastases to adrenals 42.48 22.02 16 29312 1587 110558384
Biliary obstruction 41.68 22.02 23 29305 5535 110554436
Protein induced by vitamin K absence or antagonist II increased 41.39 22.02 8 29320 55 110559916
Toxicity to various agents 41.22 22.02 40 29288 480515 110079456
Ammonia increased 40.55 22.02 26 29302 8224 110551747
Musculoskeletal stiffness 40.41 22.02 12 29316 279810 110280161
Abdominal pain upper 40.07 22.02 191 29137 348920 110211051
Treatment failure 39.83 22.02 12 29316 277222 110282749
Overdose 39.78 22.02 7 29321 233787 110326184
Rectal cancer 37.86 22.02 19 29309 3770 110556201
Osteoarthritis 37.12 22.02 3 29325 182620 110377351
Hyperbilirubinaemia 36.76 22.02 43 29285 30628 110529343
Wound 35.83 22.02 9 29319 234428 110325543
Injury 35.79 22.02 3 29325 177262 110382709
Type 2 diabetes mellitus 35.78 22.02 3 29325 177229 110382742
Pre-existing condition improved 35.67 22.02 22 29306 6504 110553467
Feeding disorder 34.42 22.02 35 29293 21327 110538644
Folliculitis 33.40 22.02 3 29325 167650 110392321
Hypersomnia 33.06 22.02 39 29289 28022 110531949
Protein urine present 32.81 22.02 26 29302 11458 110548513
Malignant neoplasm progression 32.44 22.02 111 29217 174456 110385515
Aphonia 32.28 22.02 27 29301 12833 110547138
Therapeutic product ineffective 31.87 22.02 15 29313 2589 110557382
Decreased activity 31.68 22.02 25 29303 10949 110549022
Cardiac arrest 31.15 22.02 7 29321 196746 110363225
Pulmonary cavitation 31.11 22.02 14 29314 2180 110557791
Tumour rupture 30.63 22.02 10 29318 650 110559321
Anxiety 30.42 22.02 28 29300 345050 110214921
Gait disturbance 30.31 22.02 150 29178 278058 110281913
Depression 30.11 22.02 24 29304 317311 110242660
Intestinal obstruction 29.95 22.02 52 29276 53175 110506796
Skin induration 29.73 22.02 17 29311 4378 110555593
Colorectal cancer 29.01 22.02 22 29306 9092 110550879
Abnormal loss of weight 28.83 22.02 23 29305 10234 110549737
Febrile neutropenia 28.77 22.02 25 29303 316742 110243229
Acute kidney injury 28.31 22.02 81 29247 635349 109924622
Ill-defined disorder 28.25 22.02 4 29324 156849 110403122
Hepatic lesion 28.14 22.02 21 29307 8472 110551499
Alanine aminotransferase increased 27.54 22.02 109 29219 183664 110376307
Migraine 27.39 22.02 6 29322 171646 110388325
Intentional product use issue 27.18 22.02 16 29312 247890 110312081
Food refusal 27.07 22.02 10 29318 940 110559031
Chromaturia 26.92 22.02 36 29292 29324 110530647
Arthralgia 26.25 22.02 112 29216 779520 109780451
Hepatic pain 26.12 22.02 16 29312 4674 110555297
Sleep disorder 26.09 22.02 10 29318 198634 110361337
Swelling 25.93 22.02 33 29295 351008 110208963
Hypersensitivity 25.88 22.02 42 29286 403956 110156015
Gait inability 25.58 22.02 87 29241 136289 110423682
Skin disorder 25.56 22.02 43 29285 42870 110517101
Bedridden 25.37 22.02 24 29304 13401 110546570
Hepatocellular carcinoma 25.33 22.02 21 29307 9859 110550112
Cancer pain 25.29 22.02 18 29310 6754 110553217
Metastases to bone 25.07 22.02 36 29292 31336 110528635
Discomfort 24.77 22.02 13 29315 214694 110345277
Ocular icterus 24.73 22.02 17 29311 6036 110553935
Fall 24.68 22.02 80 29248 603402 109956569
Colon cancer recurrent 24.55 22.02 6 29322 134 110559837
Psoriasis 24.23 22.02 4 29324 139989 110419982
Metastases to abdominal cavity 24.13 22.02 9 29319 869 110559102
Osteosarcoma metastatic 24.11 22.02 5 29323 51 110559920
Metastases to central nervous system 24.09 22.02 30 29298 22787 110537184
Osteosarcoma recurrent 23.90 22.02 6 29322 150 110559821
Therapeutic product effect incomplete 23.75 22.02 15 29313 223790 110336181
Nephrotic syndrome 22.90 22.02 23 29305 13808 110546163
Hypotension 22.43 22.02 68 29260 523781 110036190
Pancytopenia 22.31 22.02 14 29314 209599 110350372
Joint range of motion decreased 22.19 22.02 3 29325 121829 110438142

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EX05 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Other protein kinase inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:38637 tyrosine kinase inhibitor
CHEBI has role CHEBI:50908 hepatotoxic agent
CHEBI has role CHEBI:66981 ophthalmology drug

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

DiseaseRelationSNOMED_IDDOID
Liver cell carcinoma indication 109841003 DOID:684
Metastasis from malignant tumor of colon indication 314998002
Gastrointestinal stromal tumor indication 420120006 DOID:9253




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.41 acidic
pKa2 11.83 acidic
pKa3 12.52 acidic
pKa4 2.76 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
40MG STIVARGA BAYER HLTHCARE N203085 Sept. 27, 2012 RX TABLET ORAL 8680124 June 2, 2030 TREATMENT OF PATIENTS WITH GASTROINTESTINAL STROMAL TUMOR (GIST), INCLUDING BUT NOT LIMITED TO PATIENTS PREVIOUSLY TREATED WITH IMATINIB AND PATIENTS WITH GIST HAVING RESISTANCE TO A KIT TYROSINE KINASE INHIBITOR

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Vascular endothelial growth factor receptor 2 Kinase INHIBITOR IC50 7.90 IUPHAR CHEMBL
Serine/threonine-protein kinase B-raf Kinase INHIBITOR IC50 7.55 CHEMBL CHEMBL
Glycine receptor subunit alpha-1 Ion channel EC50 5.74 CHEMBL
Platelet-derived growth factor receptor beta Kinase IC50 8.82 CHEMBL
Tyrosine-protein kinase ABL1 Kinase Kd 6.12 CHEMBL
Mast/stem cell growth factor receptor Kit Kinase IC50 8.21 CHEMBL
Breakpoint cluster region protein Kinase Kd 6.13 CHEMBL
Ephrin type-A receptor 2 Kinase Kd 6.08 CHEMBL
RAF proto-oncogene serine/threonine-protein kinase Kinase IC50 8.82 CHEMBL
Receptor-type tyrosine-protein kinase FLT3 Kinase IC50 7.09 CHEMBL
Proto-oncogene tyrosine-protein kinase receptor Ret Kinase Kd 6.90 CHEMBL
Vascular endothelial growth factor receptor 1 Kinase IC50 8.82 CHEMBL
Vascular endothelial growth factor receptor 3 Kinase IC50 7.34 CHEMBL
Platelet-derived growth factor receptor alpha Kinase IC50 8.38 CHEMBL
Angiopoietin-1 receptor Kinase IC50 8.82 CHEMBL
LIM domain kinase 1 Kinase Kd 6.21 CHEMBL
Dual specificity protein kinase TTK Kinase Kd 5.41 CHEMBL
Mitogen-activated protein kinase 11 Kinase Kd 5.72 CHEMBL
Ephrin type-A receptor 5 Kinase Kd 5.95 CHEMBL
Mitogen-activated protein kinase 14 Kinase Kd 6.15 CHEMBL
Dual specificity protein kinase CLK1 Kinase Kd 5.68 CHEMBL
Receptor-interacting serine/threonine-protein kinase 2 Kinase Kd 6.12 CHEMBL
Epithelial discoidin domain-containing receptor 1 Kinase Kd 6.45 CHEMBL
Bifunctional epoxide hydrolase 2 Enzyme INHIBITOR IC50 9.30 CHEMBL
MAP kinase-activated protein kinase 2 Kinase Kd 6.17 CHEMBL
Cyclin-dependent kinase 17 Kinase Kd 6.14 CHEMBL
Mitogen-activated protein kinase kinase kinase MLT Kinase Kd 6.56 CHEMBL
Discoidin domain-containing receptor 2 Kinase Kd 6.38 CHEMBL
Ephrin type-A receptor 1 Kinase Kd 8.15 CHEMBL
Mitogen-activated protein kinase kinase kinase 1 Kinase Kd 6.33 CHEMBL
Fibroblast growth factor receptor 1 Kinase IC50 8.82 CHEMBL
Receptor-interacting serine/threonine-protein kinase 3 Kinase Kd 6.43 CHEMBL
ATP-binding cassette sub-family G member 2 Transporter IC50 5.52 CHEMBL
Vascular endothelial growth factor receptor 2 Kinase IC50 8.82 CHEMBL
Vascular endothelial growth factor receptor 3 Kinase IC50 8.82 CHEMBL

External reference:

IDSource
D10137 KEGG_DRUG
1019206-88-2 SECONDARY_CAS_RN
4031721 VANDF
CHEBI:68647 CHEBI
A1JCR PDB_CHEM_ID
CHEMBL1946170 ChEMBL_ID
C559147 MESH_SUPPLEMENTAL_RECORD_UI
5891 IUPHAR_LIGAND_ID
DB08896 DRUGBANK_ID
MGN125FS9D UNII
1312397 RXNORM
193440 MMSL
28887 MMSL
d07913 MMSL
014656 NDDF
702804006 SNOMEDCT_US
703808002 SNOMEDCT_US
C2980094 UMLSCUI
11167602 PUBCHEM_CID
MGN125FS9D INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Stivarga HUMAN PRESCRIPTION DRUG LABEL 1 50419-171 TABLET, FILM COATED 40 mg ORAL NDA 30 sections