DUBERMATINIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H30ClN7O2S
Molecular Weight	516.059
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(C)S(=O)(=O)C1=C(NC2=C(Cl)C=NC(NC3=CC=C(CN4CCN(C)CC4)C=C3)=N2)C=CC=C1

InChI

InChIKey=YUAALFPUEOYPNX-UHFFFAOYSA-N

InChI=1S/C24H30ClN7O2S/c1-30(2)35(33,34)22-7-5-4-6-21(22)28-23-20(25)16-26-24(29-23)27-19-10-8-18(9-11-19)17-32-14-12-31(3)13-15-32/h4-11,16H,12-15,17H2,1-3H3,(H2,26,27,28,29)

HIDE SMILES / InChI

Molecular Formula	C24H30ClN7O2S
Molecular Weight	516.059
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://clinicaltrials.gov/ct2/show/NCT03572634 | https://www.toleropharma.com/our-research/tp-0903 | https://www.ncbi.nlm.nih.gov/pubmed/29154838

HCI-2084 (wider known as TP-0903) is developing by Tolero Pharmaceuticals for the treatment of different cancers. HCI-2084 is a small molecule AXL receptor tyrosine kinase (RTK) inhibitor. AXL is involved in maintaining a mesenchymal phenotype in cancer cells that enhanced cell survival in stressed environments, and increased resistance to targeted therapies compared to epithelial cells. AXL overexpression has been observed in multiple tumor types that have acquired resistance to various agents. TP-0903 is participating in phase I/II clinical trial in patients with previously treated chronic lymphocytic leukemia (CLL). This study will investigate the safety, pharmacokinetics, pharmacodynamics, and clinical activity of TP-0903. Besides, phase I is currently being conducted in patients with advanced solid tumors in the presence of TP-0903. In addition, TP-0903 was investigated in neuroblastoma (NB) cells, where this drug makes NB cells more vulnerable to the conventional chemotherapeutics.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Tyrosine-protein kinase receptor UFO 14 Target ID: CHEMBL4895 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22247788	Inhibitor 8297	0.027 µM [IC50]
Serine/threonine-protein kinase Aurora-A 37 Target ID: CHEMBL4722 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22247788	Inhibitor 8297	3.0 nM [IC50]
Serine/threonine-protein kinase Aurora-B 28 Target ID: CHEMBL2185 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22247788	Inhibitor 8297	12.4 nM [IC50]
Tyrosine-protein kinase receptor UFO 14 Target ID: CHEMBL4895 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25673699	Inhibitor 8297

PubMed

Title	Date	PubMed
Design, Synthesis and Biological Evaluation of a Series of Novel Axl Kinase Inhibitors.	2011 Dec 8	22247788
Targeted Axl Inhibition Primes Chronic Lymphocytic Leukemia B Cells to Apoptosis and Shows Synergistic/Additive Effects in Combination with BTK Inhibitors.	2015 May 1	25673699
Chronic lymphocytic leukemia cells from ibrutinib treated patients are sensitive to Axl receptor tyrosine kinase inhibitor therapy.	2018 Dec 14	30647852
TP-0903 inhibits neuroblastoma cell growth and enhances the sensitivity to conventional chemotherapy.	2018 Jan 5	29154838

Sample Use Guides

In Vivo Use Guide

Monotherapy: PHASE 1: TP-0903 (HCI-2084) will be a 25 mg flat dose. The study drug will be administered orally once daily for 28 days (each cycle is 28 days; no drug-free period). Patients may continue to receive TP-0903 in 28-day cycles at the same dose given during Cycle 1 until they experience unacceptable toxicity or unequivocal disease progression. No intrapatient escalation of the TP-0903 dose is permitted. PHASE 2: The starting dose of TP-0903 will be the RP2D determined during Phase 1. TP 0903 will be administered orally at a fixed dose once daily for 28 days (each cycle is 28 days; no drug-free period) with repeated cycles permitted until a patient experiences unacceptable toxicity or unequivocal disease progression.

Route of Administration: Oral

Substance Class	Chemical Created by `admin` on `Sat Dec 16 11:28:30 UTC 2023` Edited by `admin` on `Sat Dec 16 11:28:30 UTC 2023`
Record UNII	14D65TV20J
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DUBERMATINIB

Official Name

English

TP0903

Code

English

dubermatinib [INN]

Common Name

English

Dubermatinib [WHO-DD]

Common Name

English

BENZENESULFONAMIDE, 2-((5-CHLORO-2-((4-((4-METHYL-1-PIPERAZINYL)METHYL)PHENYL)AMINO)-4-PYRIMIDINYL)AMINO)-N,N-DIMETHYL-

Common Name

English

DUBERMATINIB [USAN]

Common Name

English

TP-0903

Code

English

35-CHLORO-N,N,74-TRIMETHYL-2,4-DIAZA-3(4,2)-PYRIMIDINA-7(1)-PIPERAZINA-1(1),5(1,4)-DIBENZENAHEPTAPHANE-12-SULFONAMIDE

Systematic Name

English

Code System Code Type Description

FDA UNII

14D65TV20J