Exatecan Inhibitors Exatecan (DX-8951, cas 171335-80-1) is a totally synthetic analogue of the topoisomerase I-inhibitor camptothecin, which was synthesised to impart increased aqueous solubility, greater tumour efficacy, and less toxicity than camptothecin itself. Exatecan was given as i.v. infusion over 30 min at a dose of 0.5mg/m2 every day for five consecutive days, repeated every 21 days. Seventy-four percentage of cycles could be given without dose or schedule modification. The main toxicity was haematotoxicity with grade 3/4 neutropenia in 49%, grade 3/4 thrombocytopenia in 23%, and grade 3/4 anaemia in 15% of patients, respectively. The most common drug-related toxicity was neutropenia. Non-hematologic toxicities were mostly mild to moderate; the most common were nausea, vomiting and anorexia. Plasma concentrations of DX-8951 (the anhydrous form of DX-8951f) were well described using a linear 2-compartment PK model. All concentrations and dose events were simultaneously modeled and explained by the population PK model. There was no evidence of non-linearity in the elimination PK, auto-inhibition or induction of DX-8951 clearance over the five days of administration. Thirty-one patients were treated with 100 courses of exatecan at 6 dose-schedule levels. The incidence of the principal dose-limiting toxicities, neutropenia and thrombocytopenia, was unacceptably high at exatecan doses exceeding 0.15 mg/m(2)/day as a 21-day CIVI, which was determined to be the MTD for both MP and HP patients. 435.4 g/mol
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Formulation: 435.4 g/mol
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Exatecan - 171335-80-1

Exatecan

The product is for non-human research only. Not for therapeutic or veterinary use.

Catalog Number: BT-253801

CAS Number: 171335-80-1

Molecular Formula: C24H22FN3O4

Molecular Weight: 435.4 g/mol

CAS Number 171335-80-1
Product Name Exatecan
Molecular Formula C24H22FN3O4
Molecular Weight 435.4 g/mol
InChI InChI=1S/C24H22FN3O4/c1-3-24(31)14-6-18-21-12(8-28(18)22(29)13(14)9-32-23(24)30)19-16(26)5-4-11-10(2)15(25)7-17(27-21)20(11)19/h6-7,16,31H,3-5,8-9,26H2,1-2H3/t16-,24-/m0/s1
InChI Key ZVYVPGLRVWUPMP-FYSMJZIKSA-N
Isomeric SMILES CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=C5[C@H](CCC6=C5C(=CC(=C6C)F)N=C4C3=C2)N)O
IUPAC Name (10S,23S)-23-amino-10-ethyl-18-fluoro-10-hydroxy-19-methyl-8-oxa-4,15-diazahexacyclo[14.7.1.02,14.04,13.06,11.020,24]tetracosa-1,6(11),12,14,16,18,20(24)-heptaene-5,9-dione
Canonical SMILES CCC1(C2=C(COC1=O)C(=O)N3CC4=C5C(CCC6=C5C(=CC(=C6C)F)N=C4C3=C2)N)O
Description Exatecan (DX-8951, cas 171335-80-1) is a totally synthetic analogue of the topoisomerase I-inhibitor camptothecin, which was synthesised to impart increased aqueous solubility, greater tumour efficacy, and less toxicity than camptothecin itself. Exatecan was given as i.v. infusion over 30 min at a dose of 0.5mg/m2 every day for five consecutive days, repeated every 21 days. Seventy-four percentage of cycles could be given without dose or schedule modification. The main toxicity was haematotoxicity with grade 3/4 neutropenia in 49%, grade 3/4 thrombocytopenia in 23%, and grade 3/4 anaemia in 15% of patients, respectively. The most common drug-related toxicity was neutropenia. Non-hematologic toxicities were mostly mild to moderate; the most common were nausea, vomiting and anorexia. Plasma concentrations of DX-8951 (the anhydrous form of DX-8951f) were well described using a linear 2-compartment PK model. All concentrations and dose events were simultaneously modeled and explained by the population PK model. There was no evidence of non-linearity in the elimination PK, auto-inhibition or induction of DX-8951 clearance over the five days of administration. Thirty-one patients were treated with 100 courses of exatecan at 6 dose-schedule levels. The incidence of the principal dose-limiting toxicities, neutropenia and thrombocytopenia, was unacceptably high at exatecan doses exceeding 0.15 mg/m(2)/day as a 21-day CIVI, which was determined to be the MTD for both MP and HP patients.
Other CAS Number 171335-80-1
SMILES CCC1(C2=C(COC1=O)C(=O)N3CC4=C5C(CCC6=C5C(=CC(=C6C)F)N=C4C3=C2)N)O
Synonyms (1S,9S)-1-amino-9-ethyl-5-fluoro-2,3-dihydro-9-hydroxy-4-methyl-1H,12H-benzo(de)pyrano(3',4'-6,7)indolizino(1,2-b)quinoline-10,13(9H,15H)dione methanesulfonate
DX 8951
DX 8951f
DX-8951
DX-8951a
DX-8951f
exatecan
exatecan mesilate hydrate
exatecan mesylate
exatecan methanesulfonate dihydrate
Reference 1:Pharmacokinetics and pharmacodynamics of orally administered ruxolitinib (INCB018424 phosphate) in renal and hepatic impairment patients. Chen X, Shi JG, Emm T, Scherle PA, McGee RF, Lo Y, Landman RR, Punwani NG, Williams WV, Yeleswaram S.Clin Pharmacol Drug Dev. 2014 Jan;3(1):34-42. doi: 10.1002/cpdd.77. Epub 2013 Oct 19. PMID: 27128228 2:Population pharmacokinetic analysis of orally-administered ruxolitinib (INCB018424 Phosphate) in patients with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET MF). Chen X, Williams WV, Sandor V, Yeleswaram S.J Clin Pharmacol. 2013 Jul;53(7):721-30. doi: 10.1002/jcph.102. Epub 2013 May 16. PMID: 23677817 3:The effect of CYP3A4 inhibition or induction on the pharmacokinetics and pharmacodynamics of orally administered ruxolitinib (INCB018424 phosphate) in healthy volunteers. Shi JG, Chen X, Emm T, Scherle PA, McGee RF, Lo Y, Landman RR, McKeever EG Jr, Punwani NG, Williams WV, Yeleswaram S.J Clin Pharmacol. 2012 Jun;52(6):809-18. doi: 10.1177/0091270011405663. Epub 2011 May 20. PMID: 21602517 4:The pharmacokinetics, pharmacodynamics, and safety of orally dosed INCB018424 phosphate in healthy volunteers. Shi JG, Chen X, McGee RF, Landman RR, Emm T, Lo Y, Scherle PA, Punwani NG, Williams WV, Yeleswaram S.J Clin Pharmacol. 2011 Dec;51(12):1644-54. doi: 10.1177/0091270010389469. Epub 2011 Jan 21. PMID: 21257798
PubChem Compound Exatecan
Last Modified Apr 08 2022