Tamnorzatinib | CAS#1646839-59-9 | AXL inhibitor

MedKoo Cat#: 207014 | Name: Tamnorzatinib

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Tamnorzatinib, also known as ONO-7475, is a potent and orally active Axl/Mer inhibitor. ONO-7475 targets and binds to both Axl and Mer, and prevents their activity. This blocks Axl- and Mer-mediated signal transduction pathways, and inhibits proliferation and migration of Axl- and Mer-overexpressing tumor cells. Axl and Mer, both members of the TAM (Tyro3, Axl and Mer) family of RTKs, are overexpressed by many tumor cell types. They play key roles in tumor cell proliferation, survival, invasion, angiogenesis and metastasis, and their expression is associated with drug resistance and poor prognosis

Chemical Structure

Tamnorzatinib

CAS#1646839-59-9

Theoretical Analysis

MedKoo Cat#: 207014

Name: Tamnorzatinib

CAS#: 1646839-59-9

Chemical Formula: C32H26N4O6

Exact Mass: 562.1852

Molecular Weight: 562.58

Elemental Analysis: C, 68.32; H, 4.66; N, 9.96; O, 17.06

Price and Availability

Size	Price	Availability
10mg	USD 250.00	2 Weeks
25mg	USD 450.00	2 Weeks
50mg	USD 750.00	2 Weeks
100mg	USD 1,250.00	2 Weeks
200mg	USD 2,250.00	2 Weeks
500mg	USD 4,250.00	2 Weeks

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Synonym

ONO-7475; ONO 7475; ONO7475; Tamnorzatinib

IUPAC/Chemical Name

N-[5-[(6,7-Dimethoxy-4-quinolinyl)oxy]-2-pyridinyl]-1,2,5,6,7,8-hexahydro-2,5-dioxo-1-phenyl-3-quinolinecarboxamide

InChi Key

WHMMKPWGWNYYFE-UHFFFAOYSA-N

InChi Code

InChI=1S/C32H26N4O6/c1-40-28-16-21-24(17-29(28)41-2)33-14-13-27(21)42-20-11-12-30(34-18-20)35-31(38)23-15-22-25(9-6-10-26(22)37)36(32(23)39)19-7-4-3-5-8-19/h3-5,7-8,11-18H,6,9-10H2,1-2H3,(H,34,35,38)

SMILES Code

O=C(C1=CC2=C(N(C3=CC=CC=C3)C1=O)CCCC2=O)NC4=NC=C(OC5=CC=NC6=CC(OC)=C(OC)C=C56)C=C4

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Tamnorzatinib (ONO-7475) is a potent, selective, and orally active Axl/Mer inhibitor with IC50 values of 0.7 nM and 1.0 nM.

In vitro activity:

The specific Anexelekto/MER Tyrosine Kinase (AXL) inhibitor, ONO-7475, kills FLT3-mutant AML cells with targets including Extracellular- signal Regulated Kinase (ERK) and Myeloid Cell Leukemia 1 (MCL1). ONO-7475 is effective against ABT-199-resistant cells including cells that overexpress MCL1. Proteomic analyses revealed that ABT-199-resistant cells expressed elevated levels of pro-growth and anti-apoptotic proteins compared to parental cells, and that ONO-7475 reduced the expression of these proteins in both the parental and ABT-199-resistant cells. Reference: Haematologica. 2022 Jun 1;107(6):1311-1322. https://pubmed.ncbi.nlm.nih.gov/34732043/

In vivo activity:

Importantly, ONO-7475 was effective in a human FMS-like tyrosine kinase 3 with internal tandem duplication mutant murine xenograft model. Mice fed a diet containing ONO-7475 exhibited significantly longer survival and, interestingly, blocked leukemia cell infiltration in the liver. In summary, ONO-7475 effectively kills acute myeloid leukemia cells in vitro and in vivo by mechanisms that involve disruption of diverse survival and proliferation pathways. Reference: Haematologica. 2017 Dec;102(12):2048-2057. https://pubmed.ncbi.nlm.nih.gov/28912176/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	53.33
	DMSO	126.7	225.15
	DMSO:PBS (pH 7.2) (1:1)	0.5	0.89

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 562.58 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Post SM, Ma H, Malaney P, Zhang X, Aitken MJL, Mak PY, Ruvolo VR, Yasuhiro T, Kozaki R, Chan LE, Ostermann LB, Konopleva M, Carter BZ, DiNardo C, Andreeff MD, Khoury JD, Ruvolo PP. AXL/MERTK inhibitor ONO-7475 potently synergizes with venetoclax and overcomes venetoclax resistance to kill FLT3-ITD acute myeloid leukemia. Haematologica. 2022 Jun 1;107(6):1311-1322. doi: 10.3324/haematol.2021.278369. PMID: 34732043; PMCID: PMC9152975. 2. Ruvolo PP, Ma H, Ruvolo VR, Zhang X, Mu H, Schober W, Hernandez I, Gallardo M, Khoury JD, Cortes J, Andreeff M, Post SM. Anexelekto/MER tyrosine kinase inhibitor ONO-7475 arrests growth and kills FMS-like tyrosine kinase 3-internal tandem duplication mutant acute myeloid leukemia cells by diverse mechanisms. Haematologica. 2017 Dec;102(12):2048-2057. doi: 10.3324/haematol.2017.168856. Epub 2017 Sep 14. PMID: 28912176; PMCID: PMC5709104. 3. Okura N, Nishioka N, Yamada T, Taniguchi H, Tanimura K, Katayama Y, Yoshimura A, Watanabe S, Kikuchi T, Shiotsu S, Kitazaki T, Nishiyama A, Iwasaku M, Kaneko Y, Uchino J, Uehara H, Horinaka M, Sakai T, Tanaka K, Kozaki R, Yano S, Takayama K. ONO-7475, a Novel AXL Inhibitor, Suppresses the Adaptive Resistance to Initial EGFR-TKI Treatment in EGFR-Mutated Non-Small Cell Lung Cancer. Clin Cancer Res. 2020 May 1;26(9):2244-2256. doi: 10.1158/1078-0432.CCR-19-2321. Epub 2020 Jan 17. PMID: 31953310.

In vitro protocol:

In vivo protocol:

1. Okura N, Nishioka N, Yamada T, Taniguchi H, Tanimura K, Katayama Y, Yoshimura A, Watanabe S, Kikuchi T, Shiotsu S, Kitazaki T, Nishiyama A, Iwasaku M, Kaneko Y, Uchino J, Uehara H, Horinaka M, Sakai T, Tanaka K, Kozaki R, Yano S, Takayama K. ONO-7475, a Novel AXL Inhibitor, Suppresses the Adaptive Resistance to Initial EGFR-TKI Treatment in EGFR-Mutated Non-Small Cell Lung Cancer. Clin Cancer Res. 2020 May 1;26(9):2244-2256. doi: 10.1158/1078-0432.CCR-19-2321. Epub 2020 Jan 17. PMID: 31953310. 2. Ruvolo PP, Ma H, Ruvolo VR, Zhang X, Mu H, Schober W, Hernandez I, Gallardo M, Khoury JD, Cortes J, Andreeff M, Post SM. Anexelekto/MER tyrosine kinase inhibitor ONO-7475 arrests growth and kills FMS-like tyrosine kinase 3-internal tandem duplication mutant acute myeloid leukemia cells by diverse mechanisms. Haematologica. 2017 Dec;102(12):2048-2057. doi: 10.3324/haematol.2017.168856. Epub 2017 Sep 14. PMID: 28912176; PMCID: PMC5709104.

1: Okura N, Nishioka N, Yamada T, Taniguchi H, Tanimura K, Katayama Y, Yoshimura A, Watanabe S, Kikuchi T, Shiotsu S, Kitazaki T, Nishiyama A, Iwasaku M, Kaneko Y, Uchino J, Uehara H, Horinaka M, Sakai T, Tanaka K, Kozaki R, Yano S, Takayama K. ONO-7475, a Novel AXL Inhibitor, Suppresses the Adaptive Resistance to Initial EGFR-TKI Treatment in EGFR-Mutated Non-Small Lung Cancer. Clin Cancer Res. 2020 Jan 17. doi: 10.1158/1078-0432.CCR-19-2321. Epub ahead of print. PMID: 31953310. 2: Ruvolo PP, Ma H, Ruvolo VR, Zhang X, Mu H, Schober W, Hernandez I, Gallardo M, Khoury JD, Cortes J, Andreeff M, Post SM. Anexelekto/MER tyrosine kinase inhibitor ONO-7475 arrests growth and kills FMS-like tyrosine kinase 3-internal tandem duplication mutant acute myeloid leukemia cells by diverse mechanisms. Haematologica. 2017 Dec;102(12):2048-2057. doi: 10.3324/haematol.2017.168856. Epub 2017 Sep 14. PMID: 28912176; PMCID: PMC5709104.