Irinotecan hydrochloride trihydrate

Irinotecan hydrochloride is the hydrochloride salt of a semisynthetic derivative of camptothecin, a cytotoxic, quinoline-based alkaloid extracted from the Asian tree Camptotheca acuminata. Irinotecan, a prodrug, is converted to a biologically active metabolite 7-ethyl-10-hydroxy-camptothecin (SN-38) by a carboxylesterase-converting enzyme. One thousand-fold more potent than its parent compound irinotecan, SN-38 inhibits topoisomerase I activity by stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks that inhibit DNA replication and trigger apoptotic cell death.

Product information

CAS Number: 136572-09-3

Molecular Weight: 677.18

Formula: C33H45ClN4O9

Synonym:

CPT11

CPT-11

CPT 11

U101440E

HSDB 7607

HSDB-7607

HSDB7607

camptothecin-11

Camptosa

Campto

Related CAS Number:

100286-90-6 (Irinotecan HCl)

143490-53-3 (Irinotecan Lactone Impurity)

97682-44-5 (Irinotecan Free base)

1329502-92-2 (Irinotecan Carboxylate Sodium Salt)

Chemical Name: (S)-4, 11-diethyl-4-hydroxy-3, 14-dioxo-3, 4, 12, 14-tetrahydro-1H-pyrano[3', 4':6, 7]indolizino[1, 2-b]quinolin-9-yl [1, 4'-bipiperidine]-1'-carboxylate hydrochloride trihydrate.

Smiles: O.O.O.Cl.CCC1=C2C=C(C=CC2=NC2C3=CC4=C(COC(=O)[C@]4(O)CC)C(=O)N3CC=21)OC(=O)N1CCC(CC1)N1CCCCC1

InChiKey: KLEAIHJJLUAXIQ-JDRGBKBRSA-N

InChi: InChI=1S/C33H38N4O6.ClH.3H2O/c1-3-22-23-16-21(43-32(40)36-14-10-20(11-15-36)35-12-6-5-7-13-35)8-9-27(23)34-29-24(22)18-37-28(29)17-26-25(30(37)38)19-42-31(39)33(26,41)4-2;;;;/h8-9,16-17,20,41H,3-7,10-15,18-19H2,1-2H3;1H;3*1H2/t33-;;;;/m0..../s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 100 mg/mL(147.67 mM). Water: 1 mg/mL(1.47 mM).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

Irinotecan is activated to SN-38 by carboxylesterases to become able to interact with its target, topoisomerase I. Irinotecan induces similar amounts of cleavable complexes at its IC50 in LoVo cells and HT-29 cell lines. SN-38 induces a concentration-dependent formation of cleavable complexes, which is not significantly different in LoVo cells and HT-29 cell lines. Cell accumulation of Irinotecan is markedly different, reaching consistently higher levels in HT-29 cells than in LoVo cells. The lactone E-ring of Irinotecan and SN-38 hydrolyses reversibly in aqueous solutions, and the interconversion between the lactone and carboxylate forms is dependent on pH and temperature. Liver is primarily responsible for the activation of Irinotecan to SN-38. At equal concentrations of Irinotecan and SN-38 glucuronide, the rate of beta-glucuronidase-mediated SN-38 production is higher than that formed from Irinotecan in both tumour and normal tissue. Irinotecan is also converted to SN-38 in intestines, plasma and tumor tissues. Irinotecan is significantly more active in SCLC than in NSCLC cell lines, whereas no significant difference between histological types is observed with SN-38.

In Vivo:

In COLO 320 xenografts, Irinotecan induces a maximum growth inhibition of 92%. A single dose of Irinotecan significantly increases amounts of topoisomerase I covalently bound to DNA in stomach, duodenum, colon and liver. Concomitantly, the Irinotecan-treated group shows significantly higher amounts of DNA strand breaks in colon mucosa cells compared to the control group.

References:

1. Shingyoji M, et al. Cancer Sci. 2004, 95(6), 537-540.
2. Tobin P, et al. Br J Clin Pharmacol. 2006, 62(1), 122-129.
3. Pavillard V, et al. Cancer Chemother Pharmacol. 2002, 49(4), 329-335.

Products are for research use only. Not for human use.