MedKoo Biosciences, Inc.
Tel:   +1-919-636-5577    Fax:   +1-919-980-4831    Email:   sales@medkoo.com
Search
Login Register
Search
MedKoo Cat#: 406663 | Name: ML-265
Featured New

Description:

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

ML265, also known as TEPP-46, is a potent PKM2 activator induces tetramerization and reduces tumor formation and size in a mouse xenograft model. Cancer cells have altered metabolic processes compared to normal differentiated cells and the expression of the M2 isozyme of pyruvate kinase (PKM2) plays an important role in this aberrant metabolism. ML265 induces the more active tetrameric state of PKM2 and the X-ray co-crystal structure shows that the activator binds at the dimer-dimer interface between two subunits of PKM2. ML265 was tested in a H1299 mouse xenograft model and showed significant reduction in tumor size, weight, and occurrence with no apparent toxicity over the 7-week experiment.

Chemical Structure

ML-265
ML-265
CAS#1221186-53-3

Theoretical Analysis

MedKoo Cat#: 406663

Name: ML-265

CAS#: 1221186-53-3

Chemical Formula: C17H16N4O2S2

Exact Mass: 372.0715

Molecular Weight: 372.46

Elemental Analysis: C, 54.82; H, 4.33; N, 15.04; O, 8.59; S, 17.22

Price and Availability

Size Price Availability Quantity
5mg USD 90.00 Ready to ship
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,250.00 Ready to ship
500mg USD 2,450.00 Ready to ship
1g USD 3,850.00 Ready to ship
2g USD 6,450.00 2 Weeks
Show More
Bulk Inquiry
Buy Now
Add to Cart
Related CAS #
No Data
Synonym
ML265; ML-265; ML 265; CID44246499; CID-44246499; CID 44246499; NCGC00186528; NCGC 00186528; NCGC-00186528; TEPP46; TEPP 46; TEPP-46.
IUPAC/Chemical Name
6-(3-aminobenzyl)-4-methyl-2-(methylsulfinyl)-4,6-dihydro-5H-thieno[2',3':4,5]pyrrolo[2,3-d]pyridazin-5-one
InChi Key
ZWKJWVSEDISQIS-UHFFFAOYSA-N
InChi Code
InChI=1S/C17H16N4O2S2/c1-20-13-7-14(25(2)23)24-16(13)12-8-19-21(17(22)15(12)20)9-10-4-3-5-11(18)6-10/h3-8H,9,18H2,1-2H3
SMILES Code
O=C1C(N(C)C2=C3SC(S(C)=O)=C2)=C3C=NN1CC4=CC=CC(N)=C4
Appearance
Yellow 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, not in water
Shelf Life
>2 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
        
Biological target:
TEPP-46 (ML-265) is a potent and selective pyruvate kinase M2 (PKM2) activator with an AC50 of 92 nM, showing little or no effect on PKM1, PKL and PKR.
In vitro activity:
Incubation of HK2 cells with TGF‐β1 inhibited E‐cadherin expression and promoted vimentin, FSP‐1, α‐SMA, snail and SM‐22α expression compared with the control incubation, indicating EMT program activation. TEPP‐46 treatment restored the E‐cadherin level, suppressed mesenchymal proteins expression, and impeded the EMT program induced by TGF‐β1 (Figure 5a–k). TEPP‐46 also decreased TGF‐β1‐activated p‐smad3 expression (Figure 5j,k). Cross‐linking analysis revealed that TGF‐β1 treatment inhibited tetrameric PKM2 formation compared with control treatment and TEPP‐46 reversed the effects of TGF‐β1 (Figure 5l, Figure S6). Compared with the osmotic control, high‐glucose medium induced EMT; TEPP‐46 treatment reversed the EMT‐related alterations (Figure 5m,n). Co‐incubation with TGF‐β1 in high‐glucose medium produced further induction of EMT, and TEPP‐46 failed to restore E‐cadherin expression but suppressed mesenchymal markers expression (Figure 5m,n). TEPP‐46 also promoted tetrameric PKM2 formation and PK activity and decreased both HIF‐1α accumulation and lactate production. Such effects of TEPP‐46 were associated with suppression of potent glycolysis markers such as HXK2, p‐STAT3 and p‐mTOR. Overall, PKM2 activation by TEPP46 exhibited an antifibrotic effect via inhibition of aberrant glycolysis and the EMT program. Reference: J Diabetes Investig. 2021 May; 12(5): 697–709. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089020/
In vivo activity:
Streptozotocin (STZ) was utilized to induce diabetes in 8‐week‐old CD‐1 mice; 4 weeks after diabetes induction, proteinuria‐induced kidney fibrosis was developed by intraperitoneal injection of bovine serum albumin (BSA: 0.3 g/30 g BW) for 14 days; The PKM2 activator TEPP‐46 was also administered orally simultaneously. A disuccinimidyl suberate (DSS)‐based cross‐linking analysis indicated that TEPP‐46‐treated mice exhibited a higher PKM2 tetramer/dimer + monomer ratio than non‐TEPP‐46‐treated mice (Figure 4a,b). The pyruvate kinase activity was suppressed in diabetic mice and/or BSA‐injected mice compared with the control mice (Figure S4). In agreement with the high tetramer/dimer + monomer ratio, elevated PK activity was also observed in the TEPP‐46treated mice compared with the non‐TEPP‐46‐treated mice (Figure 4c). The PK activity was suppressed with high‐glucose medium incubation compared with osmotic control mannitol incubation, while TEPP‐46 restored the PK activity levels similar to those of the control (Figure 4d). Immunocytochemical analysis revealed that high‐glucose medium either with or without TGF‐β1 stimulated PKM2 nuclear localization; monomeric‐PKM2 translocated into the nucleus, aggravating dimeric‐PKM2 formation to promote the Warburg effect 13 , 24 , and TEPP‐46 restored normal PKM2 cellular localization (Figure 4e). PKM2 activation could restore the tubular phenotype via suppression of the EMT program and aberrant glycolysis, providing an alternative target to mitigate fibrosis in diabetic kidneys. Reference: J Diabetes Investig. 2021 May; 12(5): 697–709. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089020/
Solvent mg/mL mM comments
Solubility
DMSO 45.0 120.82
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 372.46 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.

Recalculate based on batch purity %
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. Liu H, Takagaki Y, Kumagai A, Kanasaki K, Koya D. The PKM2 activator TEPP-46 suppresses kidney fibrosis via inhibition of the EMT program and aberrant glycolysis associated with suppression of HIF-1α accumulation. J Diabetes Investig. 2021 May;12(5):697-709. doi: 10.1111/jdi.13478. Epub 2020 Dec 31. PMID: 33314682; PMCID: PMC8089020. 2. Lee SA, Ho C, Troxler M, Lin CY, Chung SH. Non-Metabolic Functions of PKM2 Contribute to Cervical Cancer Cell Proliferation Induced by the HPV16 E7 Oncoprotein. Viruses. 2021 Mar 8;13(3):433. doi: 10.3390/v13030433. PMID: 33800513; PMCID: PMC8001101. 3. Hu K, Yang Y, Lin L, Ai Q, Dai J, Fan K, Ge P, Jiang R, Wan J, Zhang L. Caloric Restriction Mimetic 2-Deoxyglucose Alleviated Inflammatory Lung Injury via Suppressing Nuclear Pyruvate Kinase M2-Signal Transducer and Activator of Transcription 3 Pathway. Front Immunol. 2018 Mar 2;9:426. doi: 10.3389/fimmu.2018.00426. PMID: 29552018; PMCID: PMC5840172.
In vitro protocol:
1. Liu H, Takagaki Y, Kumagai A, Kanasaki K, Koya D. The PKM2 activator TEPP-46 suppresses kidney fibrosis via inhibition of the EMT program and aberrant glycolysis associated with suppression of HIF-1α accumulation. J Diabetes Investig. 2021 May;12(5):697-709. doi: 10.1111/jdi.13478. Epub 2020 Dec 31. PMID: 33314682; PMCID: PMC8089020. 2. Lee SA, Ho C, Troxler M, Lin CY, Chung SH. Non-Metabolic Functions of PKM2 Contribute to Cervical Cancer Cell Proliferation Induced by the HPV16 E7 Oncoprotein. Viruses. 2021 Mar 8;13(3):433. doi: 10.3390/v13030433. PMID: 33800513; PMCID: PMC8001101.
In vivo protocol:
1. Hu K, Yang Y, Lin L, Ai Q, Dai J, Fan K, Ge P, Jiang R, Wan J, Zhang L. Caloric Restriction Mimetic 2-Deoxyglucose Alleviated Inflammatory Lung Injury via Suppressing Nuclear Pyruvate Kinase M2-Signal Transducer and Activator of Transcription 3 Pathway. Front Immunol. 2018 Mar 2;9:426. doi: 10.3389/fimmu.2018.00426. PMID: 29552018; PMCID: PMC5840172. 2. Liu H, Takagaki Y, Kumagai A, Kanasaki K, Koya D. The PKM2 activator TEPP-46 suppresses kidney fibrosis via inhibition of the EMT program and aberrant glycolysis associated with suppression of HIF-1α accumulation. J Diabetes Investig. 2021 May;12(5):697-709. doi: 10.1111/jdi.13478. Epub 2020 Dec 31. PMID: 33314682; PMCID: PMC8089020.
1: Zhang H, D'Alessandro A, Li M, Reisz JA, Riddle S, Muralidhar A, Bull T, Zhao L, Gerasimovskaya E, Stenmark KR. Histone deacetylase inhibitors synergize with sildenafil to suppress purine metabolism and proliferation in pulmonary hypertension. Vascul Pharmacol. 2023 Apr;149:107157. doi: 10.1016/j.vph.2023.107157. Epub 2023 Feb 26. PMID: 36849042; PMCID: PMC10067337. 2: Zhou J, Ekström P. Pyruvate Kinase 2, an Energy Metabolism Related Enzyme, May Have a Neuroprotective Function in Retinal Degeneration. ASN Neuro. 2023 Jan-Dec;15:17590914231151534. doi: 10.1177/17590914231151534. PMID: 36799552; PMCID: PMC9940218. 3: Shen MY, Di YX, Wang X, Tian FX, Zhang MF, Qian FY, Jiang BP, Zhou XP, Zhou LL. Panax notoginseng saponins (PNS) attenuate Th17 cell differentiation in CIA mice via inhibition of nuclear PKM2-mediated STAT3 phosphorylation. Pharm Biol. 2023 Dec;61(1):459-472. doi: 10.1080/13880209.2023.2173248. PMID: 36794740; PMCID: PMC9936999. 4: Ryu YC, Kim YR, Park J, Choi S, Ryu WJ, Kim GU, Kim E, Hwang Y, Kim H, Han G, Lee SH, Choi KY. Pyruvate Kinase M2 Promotes Hair Regeneration by Connecting Metabolic and Wnt/β-Catenin Signaling. Pharmaceutics. 2022 Dec 13;14(12):2774. doi: 10.3390/pharmaceutics14122774. PMID: 36559274; PMCID: PMC9781674. 5: Zhang Z, Zheng Y, Chen Y, Yin Y, Chen Y, Chen Q, Hou Y, Shen S, Lv M, Wang T. Gut fungi enhances immunosuppressive function of myeloid-derived suppressor cells by activating PKM2-dependent glycolysis to promote colorectal tumorigenesis. Exp Hematol Oncol. 2022 Nov 8;11(1):88. doi: 10.1186/s40164-022-00334-6. PMID: 36348389; PMCID: PMC9644472. 6: Gao S, Li X, Jiang Q, Liang Q, Zhang F, Li S, Zhang R, Luan J, Zhu J, Gu X, Xiao T, Huang H, Chen S, Ning W, Yang G, Yang C, Zhou H. PKM2 promotes pulmonary fibrosis by stabilizing TGF-β1 receptor I and enhancing TGF-β1 signaling. Sci Adv. 2022 Sep 23;8(38):eabo0987. doi: 10.1126/sciadv.abo0987. Epub 2022 Sep 21. PMID: 36129984; PMCID: PMC9491720. 7: Wang Z, Yu J, Hao D, Liu X, Wang X. Transcriptomic signatures responding to PKM2 activator TEPP-46 in the hyperglycemic human renal proximal epithelial tubular cells. Front Endocrinol (Lausanne). 2022 Aug 31;13:965379. doi: 10.3389/fendo.2022.965379. PMID: 36120453; PMCID: PMC9471676. 8: Huang B, Wang Q, Jiang L, Lu S, Li C, Xu C, Wang C, Zhang E, Zhang X. Shikonin ameliorated mice colitis by inhibiting dimerization and tetramerization of PKM2 in macrophages. Front Pharmacol. 2022 Aug 17;13:926945. doi: 10.3389/fphar.2022.926945. PMID: 36059938; PMCID: PMC9428403. 9: Yin B, Zhang X, Cai L, Han X, Li F. Function-preserving fat grafting in the breast: Results based on 18 years of experience. J Plast Reconstr Aesthet Surg. 2022 Sep;75(9):2996-3003. doi: 10.1016/j.bjps.2022.04.084. Epub 2022 May 2. PMID: 35853805. 10: Allen CNS, Santerre M, Arjona SP, Ghaleb LJ, Herzi M, Llewellyn MD, Shcherbik N, Sawaya BE. SARS-CoV-2 Causes Lung Inflammation through Metabolic Reprogramming and RAGE. Viruses. 2022 May 6;14(5):983. doi: 10.3390/v14050983. PMID: 35632725; PMCID: PMC9143006. 11: Zhang H, Tang J, Cao Y, Wang T. Salvianolic Acid B Suppresses Non-Small-Cell Lung Cancer Metastasis through PKM2-Independent Metabolic Reprogramming. Evid Based Complement Alternat Med. 2022 Apr 23;2022:9302403. doi: 10.1155/2022/9302403. PMID: 35502178; PMCID: PMC9056207. 12: Liu Z, Xu J, Li H, Shu J, Su G, Zhou C, Yang P. PD-1 Targeted Nanoparticles Inhibit Activated T Cells and Alleviate Autoimmunity via Suppression of Cellular Energy Metabolism Mediated by PKM2. Int J Nanomedicine. 2022 Apr 13;17:1711-1724. doi: 10.2147/IJN.S349360. PMID: 35444416; PMCID: PMC9014113. 13: Allen CNS, Arjona SP, Santerre M, De Lucia C, Koch WJ, Sawaya BE. Metabolic Reprogramming in HIV-Associated Neurocognitive Disorders. Front Cell Neurosci. 2022 Mar 28;16:812887. doi: 10.3389/fncel.2022.812887. PMID: 35418836; PMCID: PMC8997587. 14: Li M, Lu H, Wang X, Duan C, Zhu X, Zhang Y, Ge X, Ji F, Wang X, Su J, Zhang D. Pyruvate kinase M2 (PKM2) interacts with activating transcription factor 2 (ATF2) to bridge glycolysis and pyroptosis in microglia. Mol Immunol. 2021 Dec;140:250-266. doi: 10.1016/j.molimm.2021.10.017. Epub 2021 Nov 17. PMID: 34798593. 15: Wang D, Li C, Zhu Y, Song Y, Lu S, Sun H, Hao H, Xu X. TEPP-46-Based AIE Fluorescent Probe for Detection and Bioimaging of PKM2 in Living Cells. Anal Chem. 2021 Sep 21;93(37):12682-12689. doi: 10.1021/acs.analchem.1c02529. Epub 2021 Sep 10. PMID: 34505513. 16: Liu F, Ma M, Gao A, Ma F, Ma G, Liu P, Jia C, Wang Y, Donahue K, Zhang S, Ong IM, Keles S, Li L, Xu W. PKM2-TMEM33 axis regulates lipid homeostasis in cancer cells by controlling SCAP stability. EMBO J. 2021 Nov 15;40(22):e108065. doi: 10.15252/embj.2021108065. Epub 2021 Sep 6. PMID: 34487377; PMCID: PMC8591543. 17: Lv X, Zhou H, Hu K, Lin L, Yang Y, Li L, Tang L, Huang J, Shen Y, Jiang R, Wan J, Zhang L. Activation of PKM2 metabolically controls fulminant liver injury via restoration of pyruvate and reactivation of CDK1. Pharmacol Res. 2021 Oct;172:105838. doi: 10.1016/j.phrs.2021.105838. Epub 2021 Aug 20. PMID: 34425230. 18: Blum JE, Gheller BJ, Benvie A, Field MS, Panizza E, Vacanti NM, Berry D, Thalacker-Mercer A. Pyruvate Kinase M2 Supports Muscle Progenitor Cell Proliferation but Is Dispensable for Skeletal Muscle Regeneration after Injury. J Nutr. 2021 Nov 2;151(11):3313-3328. doi: 10.1093/jn/nxab251. PMID: 34383048; PMCID: PMC8562082. 19: Bertelsen LB, Hansen ESS, Sadowski T, Ruf S, Laustsen C. Hyperpolarized pyruvate to measure the influence of PKM2 activation on glucose metabolism in the healthy kidney. NMR Biomed. 2021 Nov;34(11):e4583. doi: 10.1002/nbm.4583. Epub 2021 Jul 8. PMID: 34240478. 20: O'Carroll SM, O'Neill LAJ. Targeting immunometabolism to treat COVID-19. Immunother Adv. 2021 Jun 2;1(1):ltab013. doi: 10.1093/immadv/ltab013. PMID: 34240083; PMCID: PMC8195165.