ML-265 free base · Synonyms: TEPP-46

TEPP-46 is a potent and selective pyruvate kinase M2 activator.

For research use only. Not for human or veterinary use.

Target Pyruvate Kinase

Research area Cancer

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Data Sheet SDS COA

ML-265 structure

CAS No.: 1221186-53-3

Download structure (.mol)

Pack sizes & pricing

Size	Price	SKU	Stock
100 mg	USD 400.00	BP-01857-100mg	In stock	Get quote
250 mg	USD 650.00	BP-01857-250mg	In stock	Get quote
500 mg	USD 880.00	BP-01857-500mg	In stock	Get quote
1 g	USD 1,250.00	BP-01857-1g	In stock	Get quote
5 g	Inquire	BP-01857-5g	Inquire	Inquire

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Description

TEPP-46 (ML-265) is a potent and selective pyruvate kinase M2 (PKM2) activator with an AC50 of 92 nM.

Biological activity

TEPP-46 and DASA-58 activate PKM2 by a mechanism similar to that of the endogenous activator FBP. Pre-treatment of cells with TEPP-46 or DASA-58 prevents pervanadate-induced inhibition of PKM2 activity. TEPP-46 also induces a decrease in the intracellular levels of acetyl-coA, lactate, ribose phosphate and serine. TEPP-46 inhibits LPS-induced Hif-1α and IL-1β, as well as the expression of a range of other Hif-1α-dependent genes. TEPP-46 treatment significantly downregulates the expression of the M1 markers Il12p40 and Cxcl-10. Activation of PKM2 using TEPP-46 significantly inhibits FSL-1 and CpG-induced Il1b mRNA expression. TEPP-46 inhibits Mtb-induced Il1b mRNA levels, boosts Mtb-induced levels of Il10 mRNA, and has no effect on levels of Tnf. In Vivo TEPP-46 exhibits good oral bioavailability with relatively low clearance, long half-life, and good volume of distribution-parameters that predict for drug exposure in tumor tissues. TEPP-46 at 150 mg/kg readily achieves maximal PKM2 activation measured in A549 xenograft tumors.

Identifiers

SMILES: O=C1C(N(C)C2=C3SC(S(C)=O)=C2)=C3C=NN1CC4=CC=CC(N)=C4
InChIKey: ZWKJWVSEDISQIS-UHFFFAOYSA-N

Specifications

MW (average): 372.4650
Formula: C₁₇H₁₆N₄O₂S₂
CAS No.: 1221186-53-3
Physical state: Solid
Color: White to light yellow
Shipping: 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: Powder -20℃ 2 years; In solvent -20℃ 1 month;

Solubility

Soluble in DMSO

Documents

References

[1]. Anastasiou D, et al. Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nat Chem Biol. 2012 Oct;8(10):839-847.

[2]. Palsson-McDermott EM, et al. Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the warburg effect in LPS-activated macrophages. Cell Metab. 2015 Jan 6;21(1):65-80.

[3]. Goran Hamid Mohammad, et al. Targeting Pyruvate Kinase M2 and Lactate Dehydrogenase A Is an Effective Combination Strategy for the Treatment of Pancreatic Cancer. Cancers (Basel). 2019 Sep 16;11(9):1372.

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