CABAZITAXEL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C45H57NO14
Molecular Weight	835.9324
Optical Activity	UNSPECIFIED
Defined Stereocenters	11 / 11
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12C[C@H](OC)[C@@]3(C)C(=O)[C@H](OC)C4=C(C)[C@H](C[C@@](O)([C@@H](OC(=O)C5=CC=CC=C5)[C@]3([H])[C@@]1(CO2)OC(C)=O)C4(C)C)OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C6=CC=CC=C6

InChI

InChIKey=BMQGVNUXMIRLCK-OAGWZNDDSA-N

InChI=1S/C45H57NO14/c1-24-28(57-39(51)33(48)32(26-17-13-11-14-18-26)46-40(52)60-41(3,4)5)22-45(53)37(58-38(50)27-19-15-12-16-20-27)35-43(8,36(49)34(55-10)31(24)42(45,6)7)29(54-9)21-30-44(35,23-56-30)59-25(2)47/h11-20,28-30,32-35,37,48,53H,21-23H2,1-10H3,(H,46,52)/t28-,29-,30+,32-,33+,34+,35-,37-,43+,44-,45+/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.drugbank.ca/drugs/DB06772 | https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201023s020lbl.pdf

Cabazitaxel (JEVTANA®) is an antineoplastic agent belonging to the taxane class and is used to treat people with prostate cancer that has progressed despite treatment with docetaxel. It is prepared by semi-synthesis with a precursor extracted from yew needles (10-deacetylbaccatin III). Cabazitaxel (JEVTANA®) is a microtubule inhibitor. It 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. The cell is then unable to progress further into the cell cycle, being stalled at metaphase, thus triggering apoptosis of the cancer cell.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
microtubule depolymerization 4 Target ID: GO:0007019 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201023s020lbl.pdf	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hormone-refractory metastatic prostate cancer 4 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201023s020lbl.pdf	Primary		Approved 8429	JEVTANA KIT Approved Use JEVTANA is a microtubule inhibitor indicated in combination with prednisone for treatment of patients with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing treatment regimen. Launch Date 1.27673277E12

C_max

Value	Dose	Analyte	Population
226 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/201023lbl.pdf	25 mg/m² 1 times / 3 weeks multiple, intravenous dose: 25 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	CABAZITAXEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN
233.29 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01751308	35 mg/m^2 single, intravenous dose: 35 mg/m^2 route of administration: intravenous experiment type: single co-administered:	CABAZITAXEL plasma	Homo sapiens population: unhealthy age: Children sex: food status:
204.864 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01751308	20 mg/m^2 single, intravenous dose: 20 mg/m^2 route of administration: intravenous experiment type: single co-administered:	CABAZITAXEL plasma	Homo sapiens population: unhealthy age: Children sex: food status:
283.657 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01751308	25 mg/m^2 single, intravenous dose: 25 mg/m^2 route of administration: intravenous experiment type: single co-administered:	CABAZITAXEL plasma	Homo sapiens population: unhealthy age: Children sex: food status:

AUC

Value	Dose	Analyte	Population
991 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/201023lbl.pdf	25 mg/m² 1 times / 3 weeks multiple, intravenous dose: 25 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	CABAZITAXEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN
1002.5 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01751308	35 mg/m^2 single, intravenous dose: 35 mg/m^2 route of administration: intravenous experiment type: single co-administered:	CABAZITAXEL plasma	Homo sapiens population: unhealthy age: Children sex: food status:
669.5 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01751308	20 mg/m^2 single, intravenous dose: 20 mg/m^2 route of administration: intravenous experiment type: single co-administered:	CABAZITAXEL plasma	Homo sapiens population: unhealthy age: Children sex: food status:
879 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01751308	25 mg/m^2 single, intravenous dose: 25 mg/m^2 route of administration: intravenous experiment type: single co-administered:	CABAZITAXEL plasma	Homo sapiens population: unhealthy age: Children sex: food status:

T_1/2

Value	Dose	Co-administered	Analyte	Population
96 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/201023lbl.pdf	25 mg/m² 1 times / 3 weeks multiple, intravenous dose: 25 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		CABAZITAXEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
9.5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/201023lbl.pdf			CABAZITAXEL serum	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
20 mg/m2 1 times / 3 weeks multiple, intravenous Dose: 20 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/29750396	unhealthy, 11.0 years (range: 5–17 years) n = 6 Health Status: unhealthy Condition: refractory solid tumors Age Group: 11.0 years (range: 5–17 years) Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/29750396	DLT: Febrile neutropenia... Dose limiting toxicities: Febrile neutropenia (grade 3, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/29750396
20 mg/m2 1 times / 3 weeks multiple, intravenous Dose: 20 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/22975213	unhealthy, 49 years (range: 34–67) n = 7 Health Status: unhealthy Condition: advanced solid tumours Age Group: 49 years (range: 34–67) Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/22975213	DLT: Diarrhoea, Neutropenia... Dose limiting toxicities: Diarrhoea (grade 3, 2 patients) Neutropenia (grade 4, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/22975213
25 mg/m2 1 times / 3 weeks multiple, intravenous Dose: 25 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 25 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/28058445	unhealthy, 54.0 years (range: 37–70 years) n = 6 Health Status: unhealthy Condition: advanced, non-hematologic cancer, mild hepatic impairment Age Group: 54.0 years (range: 37–70 years) Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/28058445	DLT: Febrile neutropenia, Hypophosphatemia... Dose limiting toxicities: Febrile neutropenia (grade 4, 5 patients) Hypophosphatemia (grade 3, 5 patients) Neutropenia (grade 4, 5 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/28058445
20 mg/m2 1 times / 3 weeks multiple, intravenous Dose: 20 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/28058445	unhealthy, 54.0 years (range: 48–60 years) n = 2 Health Status: unhealthy Condition: advanced, non-hematologic cancer, moderate hepatic impairment Age Group: 54.0 years (range: 48–60 years) Sex: F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/28058445	DLT: Neutropenic sepsis, Febrile neutropenia... Dose limiting toxicities: Neutropenic sepsis (grade 4, 2 patients) Febrile neutropenia (grade 3, 2 patients) Stoma site infection (grade 3, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/28058445
15 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 15 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 15 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/28058445	unhealthy, 56.0 years (range: 52–67 years) n = 7 Health Status: unhealthy Condition: advanced, non-hematologic cancer, moderate hepatic impairment Age Group: 56.0 years (range: 52–67 years) Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/28058445	Other AEs: Neutropenia, Febrile neutropenia... Other AEs: Neutropenia (57.1%) Febrile neutropenia (14.3%) Hepatic failure (14.3%) Leukopenia (28.6%) Jaundice (14.3%) Cholangitis (14.3%) Hyperbilirubinemia (14.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/28058445
20 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 20 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/28058445	unhealthy, 59.0 years (range: 18–75 years) n = 12 Health Status: unhealthy Condition: advanced, non-hematologic cancer, mild hepatic impairment Age Group: 59.0 years (range: 18–75 years) Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/28058445	Other AEs: Neutropenia, Febrile neutropenia... Other AEs: Neutropenia (25%) Febrile neutropenia (25%) Anemia (16.7%) Leukopenia (16.7%) Lymphopenia (8.3%) Diarrhoea (8.3%) Dehydration (8.3%) Platelet count decreased (16.7%) White blood cell count decreased (8.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/28058445
30 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 30 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 30 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/22975213	unhealthy, 63 years (range: 55–67 years) n = 5 Health Status: unhealthy Condition: advanced solid tumours Age Group: 63 years (range: 55–67 years) Sex: M Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/22975213	DLT: Neutropenia, Febrile neutropenia... Disc. AE: Thrombocytopenia... Dose limiting toxicities: Neutropenia (grade 4, 2 patients) Febrile neutropenia (grade 4, 1 patient) Bilirubin elevated (grade 3, 1 patient) Diarrhoea (grade 3, 1 patient) Neutropenic infection (grade 3, 1 patient) AEs leading to discontinuation/dose reduction: Thrombocytopenia (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/22975213
25 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 25 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 25 mg/m2, 1 times / 3 weeks Co-administed with:: prednisone(oral 10 mg daily) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/201023lbl.pdf	unhealthy, 68 years (range: 46-92 years) n = 371 Health Status: unhealthy Condition: hormone-refractory metastatic prostate cancer Age Group: 68 years (range: 46-92 years) Sex: M Population Size: 371 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/201023lbl.pdf	Disc. AE: Neutropenia, Renal failure... AEs leading to discontinuation/dose reduction: Neutropenia (9 patients) Renal failure (7 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/201023lbl.pdf
25 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 25 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 25 mg/m2, 1 times / 3 weeks Co-administed with:: prednisone Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000MedR.pdf Page: p. 59	unhealthy, 68 years (range: 46-92 years) n = 371 Health Status: unhealthy Condition: hormone-refractory metastatic prostate cancer Age Group: 68 years (range: 46-92 years) Sex: M Population Size: 371 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000MedR.pdf Page: p. 59	Disc. AE: Campylobacter infection, Urinary tract infection fungal... AEs leading to discontinuation/dose reduction: Campylobacter infection (6 patients) Urinary tract infection fungal (6 patients) Hematuria (5 patients) Neutropenic sepsis (5 patients) Pneumococcal sepsis (5 patients) Septic shock (5 patients) Fatigue (4 patients) Diarrhea (4 patients) Abdominal pain (3 patients) Febrile neutropenia (3 patients) Anemia (2 patients) Cardiac arrest (2 patients) Deep vein thrombosis (2 patients) Transaminases increased (2 patients) Leukopenia (2 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000MedR.pdf Page: p. 59
25 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 25 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 25 mg/m2, 1 times / 3 weeks Co-administed with:: prednisone(oral 10 mg daily) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000MedR.pdf Page: p. 59	unhealthy, 68 years (range: 46-92 years) n = 371 Health Status: unhealthy Condition: hormone-refractory metastatic prostate cancer Age Group: 68 years (range: 46-92 years) Sex: M Population Size: 371 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000MedR.pdf Page: p. 59	Disc. AE: Cellulitis, Pneumonia... AEs leading to discontinuation/dose reduction: Cellulitis (6 patients) Pneumonia (6 patients) Salmonellosis (6 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000MedR.pdf Page: p. 59
35 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose Dose: 35 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 35 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/29750396	unhealthy, 7.0 years (range: 6–18 years) n = 7 Health Status: unhealthy Condition: refractory solid tumors Age Group: 7.0 years (range: 6–18 years) Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/29750396	DLT: Febrile neutropenia... Dose limiting toxicities: Febrile neutropenia (grade 3, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/29750396
30 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 30 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 30 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/29750396	unhealthy, 9.5 years (range: 3–16 years) n = 16 Health Status: unhealthy Condition: refractory solid tumors Age Group: 9.5 years (range: 3–16 years) Sex: M+F Population Size: 16 Sources: https://pubmed.ncbi.nlm.nih.gov/29750396	Disc. AE: Anaphylactic reaction, Transaminases increased... Other AEs: Vomiting, Headache... AEs leading to discontinuation/dose reduction: Anaphylactic reaction (serious, 3 patients) Transaminases increased (grade 2, 1 patient) Other AEs: Vomiting (25%) Headache (25%) Nausea (31.3%) Diarrhea (43.8%) Dysphagia (37.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/29750396
25 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 25 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 25 mg/m2, 1 times / 3 weeks Co-administed with:: prednisone(oral 10 mg daily) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/201023lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/201023lbl.pdf	Other AEs: Neutropenia, Hypersensitivity reaction... Other AEs: Neutropenia (grade 5) Hypersensitivity reaction (severe) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/201023lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	substrate 1037 inhibitor 1767 inducer 389	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 BCRP 699 MRP1 106 MRP2 383 CYP2B6 810 CYP2C8 911 CYP3A 214 CYP1A2 1524 CYP2E1 882 CYP2C19 1478	CYP3A4/5 85 CYP2C8 693 CYP2A6 543 CYP2C19 991 CYP1A1 349 CYP1A2 1054 CYP1B1 92 CYP2B6 664 CYP2C18 138 CYP2E1 667 FMO 35 P-gp 1537 MRP1 107 MRP2 205 BCRP 561	CYP1A1 108 CYP3A 129

Drug as perpetrator

Target	Modality	Activity
CYP1A1 218	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=37 Page: (ClinPharm) 6, 37-38	no
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=37 Page: (ClinPharm) 6, 37-38	no
CYP3A 298	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=37 Page: (ClinPharm) 6, 37-38	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=36 Page: (ClinPharm) 6, 36, 37	no
MRP1 172	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=6, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=40 Page: (ClinPharm) 6, 40	no
MRP2 475	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=6, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=40 Page: (ClinPharm) 6, 40	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=6, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=40 Page: (ClinPharm) 6, 40	unlikely [IC50 10.8 uM]
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=6, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=40 Page: (ClinPharm) 6, 40	unlikely [IC50 41.8 uM]
CYP3A 298	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=36 Page: (ClinPharm) 6, 36, 37	unlikely [Ki 1.99 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=36 Page: (ClinPharm) 6, 36, 37	unlikely [Ki 130 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=36 Page: (ClinPharm) 6, 36, 37	unlikely [Ki 19.7 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=36 Page: (ClinPharm) 6, 36, 37	unlikely [Ki 3.26 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=36 Page: (ClinPharm) 6, 36, 37	unlikely [Ki 79.1 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=36 Page: (ClinPharm) 6, 36, 37	unlikely
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=36 Page: (ClinPharm) 6, 36, 37	unlikely
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=36 Page: (ClinPharm) 6, 36, 37	unlikely

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4/5 85	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=6, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=38 Page: (ClinPharm) 6, 24, 25, 36, 38	major	unlikely (co-administration study) Comment: Metabolised 80% to 90%, Recombinant isoform; Human liver microsomes; Weak CYP3A inducers prednisone or its metabolite, prednisolone, did not decrease cabazitaxel exposure (AUC) when given in combination with prednisone/prednisolone administered orally at 10-mg daily for three weeks. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=6, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=38 Page: (ClinPharm) 6, 24, 25, 36, 38
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=6 Page: (ClinPharm) 6, 24, 25, 36	minor
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=6, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=40 Page: (ClinPharm) 6, 40	no
CYP1A1 349	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=25 Page: (ClinPharm) 25	no
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=25 Page: (ClinPharm) 25	no
CYP1B1 92	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=25 Page: (ClinPharm) 25	no
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=25 Page: (ClinPharm) 25	no
CYP2B6 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=25 Page: (ClinPharm) 25	no
CYP2C18 138	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=25 Page: (ClinPharm) 25	no
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=25 Page: (ClinPharm) 25	no
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=25 Page: (ClinPharm) 25	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=25 Page: (ClinPharm) 25	no
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=25 Page: (ClinPharm) 25	no
FMO 35	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=25 Page: (ClinPharm) 25	no
MRP1 107	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=6, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=40 Page: (ClinPharm) 6, 40	no
MRP2 205	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=6, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=40 Page: (ClinPharm) 6, 40	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=6, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000ClinPharmR.pdf#page=39 Page: (ClinPharm) 6, 39	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000PharmrR.pdf#page=49 Page: 49.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:63584	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:63584
ChemicalBook	CB42517227	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB42517227
MolPort	MolPort-023-299-439	https://www.molport.com/shop/molecule-link/MolPort-023-299-439
Selleck Chemicals	cabazitaxel-jevtana	http://www.selleckchem.com/products/cabazitaxel-jevtana.html
ZINC	ZINC000085536932	http://zinc15.docking.org/substances/ZINC000085536932

PubMed

Title	Date	PubMed
Cabazitaxel.	2010 Sep	20811375
Cabazitaxel (jevtana): a novel agent for metastatic castration-resistant prostate cancer.	2012 Aug	23091336
Quantification of cabazitaxel, its metabolite docetaxel and the determination of the demethylated metabolites RPR112698 and RPR123142 as docetaxel equivalents in human plasma by liquid chromatography-tandem mass spectrometry.	2013 Apr 15	23542607
Molecular alterations and emerging targets in castration resistant prostate cancer.	2014 Mar	24418724

Patents

Sample Use Guides

In Vivo Use Guide

JEVTANA® 25 mg/m2 administered every three weeks as a one-hour intravenous infusion in combination with oral prednisone 10 mg administered daily throughout JEVTANA® treatment.

Route of Administration: Intravenous

In Vitro Use Guide

Cabazitaxel and docetaxel were tested in vitro against the cancer cell line panel at concentrations from 0.01 to 0.1 uM and in vivo against a subset of the solid tumor xenograft models at a dose of 10 or 7.5 mg/kg on an every 4 days × 3 I.V. schedule. In vitro, both cabazitaxel and docetaxel had similar potency (median relative IC50 0.47 nM and 0.88 nM, respectively) and a similar activity profile, with Ewing sarcoma cells being significantly more sensitive to both agents. In vitro sensitivity to docetaxel inversely correlated with mRNA expression for ABCB1, but the correlation with ABCB1 expression was weaker for cabazitaxel. In vivo cabazitaxel demonstrated significantly greater activity than docetaxel in five of 12 tumor models, inducing regressions in six models compared with three models for docetaxel.

Name

Type

Language

CABAZITAXEL

Official Name

English

TXD258

Code

English

CABAZITAXEL [MI]

Common Name

English

Cabazitaxel [WHO-DD]

Common Name

English

NSC-761432

Code

English

CABAZITAXEL ACETONATE [JAN]

Common Name

English

XRP6258

Code

English

CABAZITAXEL [EMA EPAR]

Common Name

English

CABAZITAXEL [USAN]

Common Name

English

CABAZITAXEL [VANDF]

Common Name

English

CABAZITAXEL [MART.]

Common Name

English

CABAZITAXEL [ORANGE BOOK]

Common Name

English

1-HYDROXY-7.BETA.,10.BETA.-DIMETHOXY-9-OXO-5.BETA.,20-EPOXYTAX-11-ENE-2.ALPHA.,4,13.ALPHA.-TRIYL 4-ACETATE 2-BENZOATE 13-((2R,3S)-3-(((TERT-BUTOXY)CARBONYL)AMINO)-2-HYDROXY-3-PHENYLPROPANOATE)

Common Name

English

XRP-6258

Code

English

TXD-258

Code

English

cabazitaxel [INN]

Common Name

English

JEVTANA

Brand Name

English

Classification Tree Code System Code

NDF-RT

N0000175085