Unesbulin free base | PTC596 | CAS#1610964-64-1 | BMI1 inhibitor

MedKoo Cat#: 533664 | Name: Unesbulin free base

Featured

Description:

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

Unesbulin, also known as PTC-596, is an inhibitor of B cell-specific Moloney murine leukemia virus integration site 1 (BMI1), which is a member of the polycomb repressive complex 1 (PRC1) that has a role in gene silencing. It inhibits proliferation of MOLM-13 acute myeloid leukemia (AML) and Rec-1 mantle cell lymphoma (MCL) cancer cells (IC50s = 22.4 and 136 nM, respectively). It also induces BMI1 degradation in, and apoptosis of, the same cells. PTC-596 reduces microtubule polymerization and induces cell cycle arrest at the G2/M phase in MM.1S multiple myeloma cells. It decreases the number of side population cells, a unique cell population with stem-like characteristics, in Rec-1 cells (IC50 = 138 nM). PTC-596 (5 mg/kg, p.o.) increases survival in a MOLM-13 mouse xenograft model.

Chemical Structure

Unesbulin free base

CAS#1610964-64-1 (free base)

Theoretical Analysis

MedKoo Cat#: 533664

Name: Unesbulin free base

CAS#: 1610964-64-1 (free base)

Chemical Formula: C19H13F5N6

Exact Mass: 420.1122

Molecular Weight: 420.35

Elemental Analysis: C, 54.29; H, 3.12; F, 22.60; N, 19.99

Price and Availability

Size	Price	Availability
1mg	USD 260.00	2 Weeks
5mg	USD 630.00	2 Weeks
10mg	USD 1,010.00	2 Weeks
25mg	USD 1,490.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

1610964-64-1 (free base) Unesbulin HCl

Synonym

PTC596; PTC-596; PTC 596; Unesbulin;

IUPAC/Chemical Name

5-Fluoro-2-(6-fluoro-2-methyl-1H-benzo[d]imidazol-1-yl)-N4-(4-(trifluoromethyl)phenyl)pyrimidine-4,6-diamine

InChi Key

TWLWOOPCEXYVBE-UHFFFAOYSA-N

InChi Code

InChI=1S/C19H13F5N6/c1-9-26-13-7-4-11(20)8-14(13)30(9)18-28-16(25)15(21)17(29-18)27-12-5-2-10(3-6-12)19(22,23)24/h2-8H,1H3,(H3,25,27,28,29)

SMILES Code

NC1=C(F)C(NC2=CC=C(C(F)(F)F)C=C2)=NC(N3C(C)=NC4=CC=C(F)C=C34)=N1

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

Instruction

View handling instruction

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	71.40
	DMSO	30.0	71.40
	Ethanol	5.0	11.90

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 420.35 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

1: Seipel K, Kopp B, Bacher U, Pabst T. BMI1-Inhibitor PTC596 in Combination with MCL1 Inhibitor S63845 or MEK Inhibitor Trametinib in the Treatment of Acute Leukemia. Cancers (Basel). 2021 Feb 2;13(3):581. doi: 10.3390/cancers13030581. PMID: 33540760; PMCID: PMC7867282. 2: Nagai Y, Mimura N, Rizq O, Isshiki Y, Oshima M, Rizk M, Saraya A, Koide S, Nakajima-Takagi Y, Miyota M, Chiba T, Oshima-Hasegawa N, Muto T, Tsukamoto S, Mitsukawa S, Takeda Y, Ohwada C, Takeuchi M, Iseki T, Nakaseko C, Lennox W, Sheedy J, Weetall M, Yokote K, Iwama A, Sakaida E. The combination of the tubulin binding small molecule PTC596 and proteasome inhibitors suppresses the growth of myeloma cells. Sci Rep. 2021 Jan 22;11(1):2074. doi: 10.1038/s41598-021-81577-x. PMID: 33483574; PMCID: PMC7822878. 3: Shapiro GI, O'Mara E, Laskin OL, Gao L, Baird JD, Spiegel RJ, Kaushik D, Weetall M, Colacino J, O'Keefe K, Branstrom A, Goodwin E, Infante J, Bedard PL, Kong R. Pharmacokinetics and Safety of PTC596, a Novel Tubulin-Binding Agent, in Subjects With Advanced Solid Tumors. Clin Pharmacol Drug Dev. 2021 Jan 13. doi: 10.1002/cpdd.904. Epub ahead of print. PMID: 33440067. 4: Zhong C, Kayamori K, Koide S, Shinoda D, Oshima M, Nakajima-Takagi Y, Nagai Y, Mimura N, Sakaida E, Yamazaki S, Iwano S, Miyawaki A, Ito R, Tohyama K, Yamaguchi K, Furukawa Y, Lennox W, Sheedy J, Weetall M, Iwama A. Efficacy of the novel tubulin polymerization inhibitor PTC-028 for myelodysplastic syndrome. Cancer Sci. 2020 Dec;111(12):4336-4347. doi: 10.1111/cas.14684. Epub 2020 Nov 2. PMID: 33037737; PMCID: PMC7734154. 5: Senthil Kumar S, Sengupta S, Zhu X, Mishra DK, Phoenix T, Dyer L, Fuller C, Stevenson CB, DeWire M, Fouladi M, Drissi R. Diffuse Intrinsic Pontine Glioma Cells Are Vulnerable to Mitotic Abnormalities Associated with BMI-1 Modulation. Mol Cancer Res. 2020 Nov;18(11):1711-1723. doi: 10.1158/1541-7786.MCR-20-0099. Epub 2020 Aug 14. PMID: 32801164. 6: Bolomsky A, Muller J, Stangelberger K, Lejeune M, Duray E, Breid H, Vrancken L, Pfeiffer C, Hübl W, Willheim M, Weetall M, Branstrom A, Zojer N, Caers J, Ludwig H. The anti-mitotic agents PTC-028 and PTC596 display potent activity in pre-clinical models of multiple myeloma but challenge the role of BMI-1 as an essential tumour gene. Br J Haematol. 2020 Sep;190(6):877-890. doi: 10.1111/bjh.16595. Epub 2020 Mar 30. PMID: 32232850. 7: Flamier A, Abdouh M, Hamam R, Barabino A, Patel N, Gao A, Hanna R, Bernier G. Off-target effect of the BMI1 inhibitor PTC596 drives epithelial-mesenchymal transition in glioblastoma multiforme. NPJ Precis Oncol. 2020 Jan 6;4:1. doi: 10.1038/s41698-019-0106-1. PMID: 31934644; PMCID: PMC6944693. 8: Eberle-Singh JA, Sagalovskiy I, Maurer HC, Sastra SA, Palermo CF, Decker AR, Kim MJ, Sheedy J, Mollin A, Cao L, Hu J, Branstrom A, Weetall M, Olive KP. Effective Delivery of a Microtubule Polymerization Inhibitor Synergizes with Standard Regimens in Models of Pancreatic Ductal Adenocarcinoma. Clin Cancer Res. 2019 Sep 15;25(18):5548-5560. doi: 10.1158/1078-0432.CCR-18-3281. Epub 2019 Jun 7. PMID: 31175095. 9: Barbosa K, Deshpande A, Chen BR, Ghosh A, Sun Y, Dutta S, Weetall M, Dixon J, Armstrong SA, Bohlander SK, Deshpande AJ. Acute myeloid leukemia driven by the CALM-AF10 fusion gene is dependent on BMI1. Exp Hematol. 2019 Jun;74:42-51.e3. doi: 10.1016/j.exphem.2019.04.003. Epub 2019 May 13. PMID: 31022428. 10: Maeda A, Nishida Y, Weetall M, Cao L, Branstrom A, Ishizawa J, Nii T, Schober WD, Abe Y, Matsue K, Yoshimura M, Kimura S, Kojima K. Targeting of BMI-1 expression by the novel small molecule PTC596 in mantle cell lymphoma. Oncotarget. 2018 Jun 19;9(47):28547-28560. doi: 10.18632/oncotarget.25558. PMID: 29983879; PMCID: PMC6033370. 11: Nishida Y, Maeda A, Kim MJ, Cao L, Kubota Y, Ishizawa J, AlRawi A, Kato Y, Iwama A, Fujisawa M, Matsue K, Weetall M, Dumble M, Andreeff M, Davis TW, Branstrom A, Kimura S, Kojima K. The novel BMI-1 inhibitor PTC596 downregulates MCL-1 and induces p53-independent mitochondrial apoptosis in acute myeloid leukemia progenitor cells. Blood Cancer J. 2017 Feb 17;7(2):e527. doi: 10.1038/bcj.2017.8. PMID: 28211885; PMCID: PMC5386342.

View History

DS-437