Name: Rebastinib
Brand: BOC Sciences
Price: 299 USD
Availability: MadeToOrder

Size

Price

Stock

Quantity

50 mg

$299

In stock

Purity

≥98%

Appearance

Off-White Solid

Application

Antineoplastic Agents

IUPACName

4-[4-[(5-tert-butyl-2-quinolin-6-ylpyrazol-3-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide

Synonyms

DCC2036; DCC-2036; DCC 2036; Rebastinib. 4-[4-[(5-tert-butyl-2-quinolin-6-ylpyrazol-3-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide

Melting Point

>181°C (dec.)

InChI Key

WVXNSAVVKYZVOE-UHFFFAOYSA-N

InChI

InChI=1S/C30H28FN7O3/c1-30(2,3)26-17-27(38(37-26)19-7-9-23-18(14-19)6-5-12-33-23)36-29(40)35-24-10-8-20(15-22(24)31)41-21-11-13-34-25(16-21)28(39)32-4/h5-17H,1-4H3,(H,32,39)(H2,35,36,40)

Canonical SMILES

CC(C)(C)C1=NN(C(=C1)NC(=O)NC2=C(C=C(C=C2)OC3=CC(=NC=C3)C(=O)NC)F)C4=CC5=C(C=C4)N=CC=C5

1.BCR-ABL1 compound mutations combining key kinase domain positions confer clinical resistance to ponatinib in Ph chromosome-positive leukemia.

Zabriskie MS1, Eide CA2, Tantravahi SK3, Vellore NA4, Estrada J1, Nicolini FE5, Khoury HJ6, Larson RA7, Konopleva M8, Cortes JE8, Kantarjian H8, Jabbour EJ8, Kornblau SM8, Lipton JH9, Rea D10, Stenke L11, Barbany G12, Lange T13, Hernández-Boluda JC14, Oss Cancer Cell. 2014 Sep 8;26(3):428-42. doi: 10.1016/j.ccr.2014.07.006. Epub 2014 Aug 14.

Ponatinib is the only currently approved tyrosine kinase inhibitor (TKI) that suppresses all BCR-ABL1 single mutants in Philadelphia chromosome-positive (Ph(+)) leukemia, including the recalcitrant BCR-ABL1(T315I) mutant. However, emergence of compound mutations in a BCR-ABL1 allele may confer ponatinib resistance. We found that clinically reported BCR-ABL1 compound mutants center on 12 key positions and confer varying resistance to imatinib, nilotinib, dasatinib, ponatinib, rebastinib, and bosutinib. T315I-inclusive compound mutants confer high-level resistance to TKIs, including ponatinib. In vitro resistance profiling was predictive of treatment outcomes in Ph(+) leukemia patients. Structural explanations for compound mutation-based resistance were obtained through molecular dynamics simulations. Our findings demonstrate that BCR-ABL1 compound mutants confer different levels of TKI resistance, necessitating rational treatment selection to optimize clinical outcome.

ConcentrationVolumeMass	1 mg	5 mg	10 mg
1 mM	1.8064 mL	9.0320 mL	18.0639 mL
5 mM	0.3613 mL	1.8064 mL	3.6128 mL
10 mM	0.1806 mL	0.9032 mL	1.8064 mL
50 mM	0.0361 mL	0.1806 mL	0.3613 mL

Dear Sirs, can you explain the mechanism of action of Rebastinib?

Rebastinib inhibition of angiopoietin/Tie2 signaling impairs multiple pathways in tumor progression mediated by protumoral Tie2+ macrophages, including TMEM-dependent dissemination and angiopoietin/Tie2-dependent angiogenesis.

5/4/2016

Your help will be highly appreciated. How does Rebastinib inhibit both u-ABL1T315I and p-ABL1T315I?

Rebastinib potently inhibits both u-ABL1T315I (IC50 5 nM) and p-ABL1T315I (IC50 4 nM), both of which exist predominately in the Type I conformation due to stabilization of an activating hydrophobic spine by the T315I mutation.

27/11/2016

Do you have any information about how Rebastinib reduces tumor growth and metastasis?

Rebastinib reduces tumor growth and metastasis in an orthotopic mouse model of metastatic mammary carcinoma through reduction of Tie2+ myeloid cell infiltration, antiangiogenic effects, and blockade of tumor cell intravasation mediated by perivascular Tie2Hi/Vegf-AHi macrophages in the tumor microenvironment of metastasis (TMEM).

13/5/2022

inhibit the SRC family kinases LYN, SRC, FGR, and HCK, and PDGFRα, and PDGFRβ

In my lab, Rebastinib greatly inhibits the SRC family kinases LYN, SRC, FGR, and HCK, and PDGFRα, and PDGFRβ with IC50 of 29±1, 34±6, 38±1, 40±1, 70±10 and 113±10 nM, respectively. Good job.

7/12/2020

inhibit p-ABL1native

We observed that Rebastinib strongly inhibits p-ABL1native (IC50 2 nM), which more readily adopts an active, Type I conformation. Worked adequately.

3/4/2022

inhibit the proliferation of Ba/F3 cells

In our laboratory, Rebastinib effectively inhibits the proliferation of Ba/F3 cells expressing native BCR-ABL1native (IC50 5.4 nM). Rebastinib also inhibits proliferation of the Ph+ cell line K562 (IC50 5.5 nM). Working well in the lab.

7/10/2022

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* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂