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

Stem definitionDrug idCAS RN
antineoplastics, taxane derivatives 4153 183133-96-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • cabazitaxel
  • jevtana
  • RPR-116258A
  • XRP-6258
  • cabazitaxel acetonate
  • cabazitaxel acetone
  • javtana
a microtubule inhibitor, cabazitaxel binds to tubulin and promotes its assembly into microtubules while simultaneously inhibiting disassembly. This leads to the stabilization of microtubules, which results in the inhibition of mitotic and interphase cellular functions
  • Molecular weight: 835.94
  • Formula: C45H57NO14
  • CLOGP: 4.59
  • LIPINSKI: 3
  • HAC: 15
  • HDO: 3
  • TPSA: 202.45
  • ALOGS: -5.31
  • ROTB: 15
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
Vd (Volume of distribution) 48 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 11 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.24 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 74.50 hours Lombardo F, Berellini G, Obach RS
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 3.938 Moderate 0.79
caco2-efflux Caco-2 efflux ratio (BA/AB) 2.466 Moderate 0.79
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 47.753 10^-6 cm/s Moderate 0.79
dh-clint Dog hepatocyte intrinsic clearance 32.810 uL/min/10^6 cells Moderate 0.79
dppb Dog plasma protein binding (% unbound) 2.610 % Moderate 0.79
fcs-ppb Fetal calf serum protein binding (% unbound) 7.450 % Moderate 0.79
herg hERG pIC50 4.766 pIC50 Moderate 0.79
hh-clint Human hepatocyte intrinsic clearance 10.990 uL/min/10^6 cells Moderate 0.79
hlm-clint Human liver microsomal intrinsic clearance 81.096 uL/min/mg protein Moderate 0.79
hppb Human plasma protein binding (% unbound) 4.720 % Moderate 0.79
kinase-safety-class ACVR2B,AXL,BRAF,BTK,CAMK2D,CDK5,CDK9,EIF2AK3,EPHB4,ERBB2,GRK2,ITK,MAPK7,NTRK2,PDK1,PDK2,PDK4,PIK3CB,PRKDC,TEK 20
kinase-selectivity-class AXL,GRK2 2
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 5.236 Moderate 0.72
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 2.178 Moderate 0.79
mh-clint Mouse hepatocyte intrinsic clearance 36.898 Moderate 0.79
mppb Mouse plasma protein binding (% unbound) 2.250 Moderate 0.79
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 17.258 Moderate 0.79
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 5.220 % Moderate 0.79
rat-kpuu-brain Rat brain Kpuu 0.008 % Moderate 0.72
rh-clint Rat hepatocyte intrinsic clearance 29.923 uL/min/10^6 cells Moderate 0.79
rh-fuinc Rat hepatocyte fraction unbound in incubation 20 % Moderate 0.79
rppb Rat plasma protein binding (% unbound) 2.910 % Moderate 0.79
solubility-dd Solubility at pH 7.4 in DMSO 5.433 uM Moderate 0.79

Approvals:

DateAgencyCompanyOrphan
June 17, 2010 FDA SANOFI AVENTIS US
March 17, 2011 EMA Sanofi Winthrop Industrie

FDA Adverse Event Reporting System (Female)

None

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
Ureteritis 456.68 25.12 67 7544 85 42613639
Prostatic specific antigen increased 374.45 25.12 133 7478 16792 42596932
Metastases to bone 277.52 25.12 103 7508 14706 42599018
Malignant neoplasm progression 229.05 25.12 174 7437 108226 42505498
Febrile neutropenia 192.58 25.12 199 7412 185504 42428220
Hydronephrosis 173.76 25.12 69 7542 11796 42601928
Prostate cancer metastatic 165.23 25.12 57 7554 6572 42607152
Hormone-refractory prostate cancer 160.47 25.12 37 7574 967 42612757
Metastases to lymph nodes 158.95 25.12 54 7557 5944 42607780
Haematuria 149.49 25.12 105 7506 57694 42556030
Osteonecrosis of jaw 148.43 25.12 71 7540 18978 42594746
Hydroureter 118.79 25.12 25 7586 422 42613302
Disease progression 105.72 25.12 129 7482 143527 42470197
Neutropenia 82.51 25.12 136 7475 199295 42414429
Colony stimulating factor therapy 75.51 25.12 15 7596 187 42613537
Bone lesion 60.80 25.12 23 7588 3443 42610281
Prostate cancer 59.35 25.12 55 7556 44588 42569136
Metastases to lung 58.19 25.12 32 7579 11392 42602332
BRCA2 gene mutation 56.72 25.12 10 7601 61 42613663
Neutrophil count decreased 56.62 25.12 63 7548 63352 42550372
BRCA1 gene mutation 56.31 25.12 10 7601 64 42613660
Anaemia 52.53 25.12 138 7473 280140 42333584
Prostate cancer recurrent 46.16 25.12 14 7597 1069 42612655
Metastases to liver 42.90 25.12 30 7581 16296 42597428
Necrotising retinitis 38.33 25.12 12 7599 1018 42612706
Prostatic specific antigen abnormal 35.37 25.12 11 7600 913 42612811
Metastases to soft tissue 33.38 25.12 9 7602 450 42613274
Peri-implantitis 32.94 25.12 7 7604 124 42613600
Bone pain 32.93 25.12 30 7581 23762 42589962
Pulmonary embolism 31.09 25.12 67 7544 119545 42494179
Septic shock 30.59 25.12 57 7554 91615 42522109
Onycholysis 26.42 25.12 9 7602 996 42612728
Thrombocytopenia 25.27 25.12 83 7528 190196 42423528

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
Prostatic specific antigen increased 428.89 27.67 107 6309 12404 110570479
Febrile neutropenia 228.38 27.67 170 6246 316597 110266286
Metastases to bone 187.66 27.67 70 6346 31302 110551581
Malignant neoplasm progression 128.36 27.67 95 6321 174472 110408411
Osteonecrosis of jaw 124.16 27.67 59 6357 47958 110534925
Metastases to lymph nodes 117.87 27.67 41 6375 14991 110567892
Prostate cancer metastatic 105.23 27.67 29 6387 4914 110577969
Neutropenia 100.70 27.67 116 6300 374504 110208379
Disease progression 98.60 27.67 94 6322 243940 110338943
Prostate cancer 84.49 27.67 42 6374 37599 110545284
Haematuria 83.96 27.67 55 6361 82950 110499933
Hydronephrosis 77.68 27.67 33 6383 20632 110562251
Neutrophil count decreased 71.73 27.67 58 6358 120883 110462000
Prostate cancer recurrent 57.93 27.67 13 6403 949 110581934
Bone lesion 54.27 27.67 19 6397 7068 110575815
Hormone-refractory prostate cancer 53.18 27.67 12 6404 898 110581985
Colony stimulating factor therapy 51.62 27.67 11 6405 631 110582252
Anaemia 51.58 27.67 104 6312 546982 110035901
Necrotising retinitis 46.48 27.67 12 6404 1584 110581299
Septic shock 45.96 27.67 51 6365 157477 110425406
Pyrexia 44.24 27.67 133 6283 898132 109684751
Sepsis 41.83 27.67 71 6345 327275 110255608
Pulmonary embolism 40.83 27.67 56 6360 214418 110368465
Peri-implantitis 37.33 27.67 7 6409 208 110582675
Metastases to liver 37.10 27.67 24 6392 35362 110547521
Prostatic specific antigen decreased 35.66 27.67 6 6410 94 110582789
Peripheral sensory neuropathy 35.61 27.67 18 6398 16662 110566221
Metastases to soft tissue 34.10 27.67 8 6408 711 110582172
Disseminated intravascular coagulation 31.45 27.67 23 6393 41263 110541620
Interstitial lung disease 30.53 27.67 39 6377 139295 110443588
Metastases to lung 30.15 27.67 18 6398 23045 110559838
Dysuria 27.72 27.67 25 6391 60206 110522677

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01CD04 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PLANT ALKALOIDS AND OTHER NATURAL PRODUCTS
Taxanes
FDA PE N0000175085 Microtubule Inhibition
FDA EPC N0000175592 Microtubule Inhibitor
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:61950 microtubule-stabilising agent

Related Drugs by ATC class:

L01CD Taxanes 2 drugs
docetaxelpaclitaxel

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

DiseaseRelationSNOMED_IDDOID
Metastatic Prostate Carcinoma indication
Nutritional disorder contraindication 2492009 DOID:374
Asthenia contraindication 13791008
Hyperbilirubinemia contraindication 14783006 DOID:2741
Nausea and vomiting contraindication 16932000
Dehydration contraindication 34095006
Acute nephropathy contraindication 58574008
Acute infectious disease contraindication 63171007
Leukopenia contraindication 84828003 DOID:615
Kidney disease contraindication 90708001 DOID:557
Liver function tests abnormal contraindication 166603001
Disease of liver contraindication 235856003 DOID:409
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Neutropenic disorder contraindication 303011007 DOID:1227
Severe diarrhea contraindication 409587002
Breastfeeding (mother) contraindication 413712001
Radiation Therapy Involving Bone contraindication




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 10.2 acidic
pKa2 12.4 acidic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
60MG/1.5ML (40MG/ML) JEVTANA KIT SANOFI AVENTIS US N201023 June 17, 2010 RX SOLUTION INTRAVENOUS 10583110 Oct. 27, 2030 INCREASING SURVIVAL IN METASTATIC CASTRATION-RESISTANT PROSTATE CANCER PATIENTS PREVIOUSLY TREATED WITH DOCETAXEL BY ADMINISTERING AS A 3 WEEK CYCLE CABAZITAXEL AFTER 5 MG DEXCHLORPHENIRAMINE, 8 MG DEXAMETHASONE, AND AN H2-ANTAGONIST
60MG/1.5ML (40MG/ML) JEVTANA KIT SANOFI AVENTIS US N201023 June 17, 2010 RX SOLUTION INTRAVENOUS 10716777 Oct. 27, 2030 INCREASING SURVIVAL IN METASTATIC CASTRATION-RESISTANT PROSTATE CANCER PATIENTS PREVIOUSLY TREATED WITH DOCETAXEL BY ADMINISTERING 20 TO 25 MG/M2 CABAZITAXEL AFTER A PREMEDICATION REGIMEN THAT INCLUDES AN H2-ANTAGONIST
60MG/1.5ML (40MG/ML) JEVTANA KIT SANOFI AVENTIS US N201023 June 17, 2010 RX SOLUTION INTRAVENOUS 12453712 Oct. 27, 2030 INCREASING SURVIVAL IN MCRPC PATIENTS PREVIOUSLY TREATED WITH DOCETAXEL BY ADMINISTERING CABAZITAXEL IN COMBINATION WITH PREDNISONE OR PREDNISOLONE AFTER A PREMEDICATION REGIMEN THAT INCLUDES AN ANTIHISTAMINE
60MG/1.5ML (40MG/ML) JEVTANA KIT SANOFI AVENTIS US N201023 June 17, 2010 RX SOLUTION INTRAVENOUS 8927592 Oct. 27, 2030 INCREASING SURVIVAL IN MCRPC PATIENTS PREVIOUSLY TREATED WITH DOCETAXEL BY ADMINISTERING CABAZITAXEL IN COMBINATION WITH PREDNISONE OR PREDNISOLONE AFTER A PREMEDICATION REGIMEN THAT INCLUDES AN ANTIHISTAMINE, A CORTICOSTEROID, AND AN H2-ANTAGONIST

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Tubulin beta Tumour-associated antigen INHIBITOR SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE

External reference:

IDSource
4030043 VUID
N0000181529 NUI
D09755 KEGG_DRUG
4030043 VANDF
C2830183 UMLSCUI
CHEBI:63584 CHEBI
CHEMBL1201748 ChEMBL_ID
DB06772 DRUGBANK_ID
C552428 MESH_SUPPLEMENTAL_RECORD_UI
6798 IUPHAR_LIGAND_ID
8967 INN_ID
1426815-65-7 SECONDARY_CAS_RN
51F690397J UNII
9854073 PUBCHEM_CID
996051 RXNORM
173956 MMSL
27256 MMSL
d07658 MMSL
013461 NDDF
446706007 SNOMEDCT_US
447182009 SNOMEDCT_US
C532412 MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

None