MERTANSINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C35H48ClN3O10S
Molecular Weight	738.288
Optical Activity	UNSPECIFIED
Defined Stereocenters	8 / 8
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12O[C@@]1(C)[C@H](CC(=O)N(C)C3=C(Cl)C(OC)=CC(C\C(C)=C\C=C\[C@@H](OC)[C@@]4(O)C[C@]([H])(OC(=O)N4)[C@H]2C)=C3)OC(=O)[C@H](C)N(C)C(=O)CCS

InChI

InChIKey=ANZJBCHSOXCCRQ-FKUXLPTCSA-N

InChI=1S/C35H48ClN3O10S/c1-19-10-9-11-26(46-8)35(44)18-25(47-33(43)37-35)20(2)31-34(4,49-31)27(48-32(42)21(3)38(5)28(40)12-13-50)17-29(41)39(6)23-15-22(14-19)16-24(45-7)30(23)36/h9-11,15-16,20-21,25-27,31,44,50H,12-14,17-18H2,1-8H3,(H,37,43)/b11-9+,19-10+/t20-,21+,25+,26-,27+,31+,34+,35+/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20937594

Mertansine (Maytansine) is a 19–member ansa macrolide structure attached to a chlorinated benzenering. It was originally isolated from the shrub Maytenus ovatus. Mertansine (DM1) is a tubulin inhibitor, it inhibits the assembly of microtubules by binding to tubulin, with a linker structure can create an antibody-drug conjugate (ADC). Mertansine is a potent microtubule-targeted compound that induces mitotic arrest and kills tumor cells at sub-nanomolar concentrations. The antimitotic effect of maytansine has been attributed to its ability to inhibit microtubule assembly by binding to tubulin with a KD of ~ 1 umol/L, at or near the vinblastine-binding site. Experimental ADCs with the SPP-DM1 design include lorvotuzumab mertansine. DM1 can also be linked to an antibody using the SMCC (4-(3-mercapto-2,5-dioxo-1-pyrrolidinylmethyl)-cylohexanecarboxylic acid) linker, in which case the International Nonproprietary Name of the conjugate formed contains the word emtansine. DM1 and its attachment via these linkers result from ImmunoGen Inc research. Trastuzumab emtansine (T-DM1) is an anti-HER2/neu antibody-drug conjugate.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tubulin 69 Target ID: CHEMBL2095182 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20937594	Inhibitor 8297		0.86 µM [Kd]

Conditions

Condition	Modality	Highest Phase	Product
Leukemia 87 Sources: https://clinicaltrials.gov/ct2/show/NCT02420873 http://adisinsight.springer.com/drugs/800008504	Primary	Phase II 1132	Unknown Approved Use Unknown
Solid tumors 145 Sources: https://clinicaltrials.gov/ct2/show/NCT02452554 http://adisinsight.springer.com/drugs/800008504	Primary	Phase II 1132	Unknown Approved Use Unknown
Breast cancer 434 Sources: https://clinicaltrials.gov/ct2/show/NCT01745965	Primary	Phase II 1132	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781 supressor 21 inhibitor 1587	supressor 19 substrate 1037	inhibitor 1852 substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
UGT1A4 77 CYP3A5 73 UGT1A6 108 UGT1A1 204 CYP2C8 911 UGT1A9 116 UGT1A3 84 UGT2B7 146 P-gp 1461	CYP3A4/5 85 CYP1A2 1054 CYP2B6 664 CYP2C8 693 P-gp 1537 CYP2C19 991 CYP2E1 667

Drug as perpetrator

Target	Modality	Activity
UGT1A4 80	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/32131538/	no [IC50 >2.5 uM]
CYP3A4 1925	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/32131538/	no
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/25048520/	no
UGT1A6 141	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32131538/	no
UGT1A9 121	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32131538/	no
UGT2B7 157	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32131538/	no
CYP2C8 965	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/32131538/	yes [IC50 0.0321 uM]
CYP2B6 1001	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/32131538/	yes [IC50 0.0368 uM]
UGT1A9 121	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/32131538/	yes [IC50 0.0541 uM]
CYP1A2 1692	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/32131538/	yes [IC50 0.0937 uM]
CYP3A4 1925	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/32131538/	yes [IC50 0.16 uM]
CYP2C9 1819	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/32131538/	yes [IC50 0.5784 uM]
UGT1A1 254	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/32131538/	yes [IC50 0.8567 uM]
UGT1A3 93	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32131538/	yes [IC50 4.3 uM]
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32131538/ \| https://pubmed.ncbi.nlm.nih.gov/25048520/	yes [Ki 11 uM]
UGT1A1 254	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32131538/	yes [Ki 13.5 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32131538/ \| https://pubmed.ncbi.nlm.nih.gov/25048520/	yes [Ki 14 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32131538/ \| https://pubmed.ncbi.nlm.nih.gov/25048520/	yes [Ki 3.4 uM]
CYP2C19 1553	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/32131538/	yes
CYP3A5 130	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/25048520/	yes
UGT1A4 80	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32131538/	yes

Drug as victim

Target	Modality	Activity
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22752008/	no
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22752008/	no
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22752008/	no
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22752008/	no
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22752008/	no
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22752008/	no
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25048520/	yes
CYP3A4/5 85	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25048520/	yes
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25048520/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/24035823/

Sourcing

Vendor/Aggregator	ID	URL
AbovChem LLC	HY-19792	http://www.abovchem.com/pc/en/product_list.aspx?wd=HY-19792
eMolecules	93428809	https://orderbb.emolecules.com/search/#?query=93428809

PubMed

Title	Date	PubMed
Maytansine and cellular metabolites of antibody-maytansinoid conjugates strongly suppress microtubule dynamics by binding to microtubules.	2010 Oct	20937594

Patents

Sample Use Guides

In Vivo Use Guide

Leukemia treatment: Lorvotuzumab mertansine (IMGN901) administered intravenously at a dose of 100 mg/m2 on Day 1 and 8 of a 21-day cycle.

Route of Administration: Intravenous

In Vitro Use Guide

Under the experimental conditions used, the half maximal concentration for inhibition of microtubule assembly for Mertansine (Maytansine) was 1 ± 0.02 umol/L; for S-methyl DM1, 4 ± 0.1 umol/L; and for S-methyl DM4, 1.7 ± 0.4 umol/L. Maytansine showed nearly complete inhibition of microtubule polymerization at 3 umol/L.

Name

Type

Language

MERTANSINE

Common Name

English

MAYTANSINE, N2'-DEACETYL-N2'-(3-MERCAPTO-1-OXOPROPYL)-

Common Name

English

DM1

Common Name

English

N2'-DEACETYL-N2'-(3-MERCAPTO-1-OXOPROPYL)-MAYTANSINE

Common Name

English

MAYTANSINOID DM1 [MI]

Common Name

English

MAYTANSINOID DM 1

Common Name

English

N2'-DEACETYL-N2'-(3-MERCAPTO-1-OXOPROPYL)-MAYTANSINE, L-

Common Name

English

DM-1

Common Name

English

Code System Code Type Description

FDA UNII

DDZ29HGH0E