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505487

Sigma-Aldrich

TEPP-46

≥98% (HPLC), solid, PKM2 activator, Calbiochem®

Synonym(s):

PKM2 Activator IV, TEPP-46, 6-((3-Aminophenyl)methyl)-4-methyl-2-methylsulfinylthieno[3,4]pyrrolo[1,3-d]pyridazin-5-one, Pyruvate Kinase M2 Activator IV, ML265, NCGC00186528, TEPP46, Pyruvate Kinase M2 Activator IV, ML265, NCGC00186528, TEPP46, 6-((3-Aminophenyl)methyl)-4-methyl-2-methylsulfinylthieno[3,4]pyrrolo[1,3-d]pyridazin-5-one

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About This Item

Empirical Formula (Hill Notation):
C17H16N4O2S2
CAS Number:
1221186-53-3
Molecular Weight:
372.46
UNSPSC Code:
12352200
NACRES:
NA.77

product name

PKM2 Activator IV, TEPP-46,

Assay

≥98% (HPLC)

Quality Level

100

form

solid

manufacturer/tradename

Calbiochem®

storage condition

OK to freeze
protect from light

color

white

solubility

DMSO: 100 mg/mL

shipped in

ambient

storage temp.

2-8°C

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

InChI key

ZWKJWVSEDISQIS-UHFFFAOYSA-N

General description

A cell-permeable thienopyrrolopyridazinone that acts as a potent allosteric PKM2 activator (AC50 = 92 nM; [PKM2] = 0.1 nM) via stoichiometric interaction (Two activator molecules per tetramer) with FBP-bound PKM2 tetramer (One FBP per monomer) in a similar manner as PKM2 Activator III (Cat. No. 504537), resulting in highly stabilized PKM2 tetramer resistant to dissociation in the presence of phosphotyrosine-containing peptide/protein or upon PKM2 K305Q mutation. Reported to exhibit good aqueous solubility (29.6 µg/mL or 79.5 µM in PBS, pH 7.4) and retard human lung carcinoma H1299 proliferation under hypoxia, but not normoxia, condition in cultures (doubling time = 50 and 35 h, respectively, with or without 30 µM TEPP-46; 1% O2) in vitro. TEPP-46 is bioavailable in mice via i.p. (Tmax = 0.5 h; Cmax = 10.854 µg/mL; AUCINF = 26.994 hr·µg/mL; 10 mg/kg) or p.o. (Tmax = 0.25 h; Cmax = 10.179 µg/mL; AUCINF = 24.350 hr·µg/mL; 10 mg/kg) administration and shown to impair H1299 tumorigenesis in mice (%tumor development/av. tumor weight = 30%/0.13 mg and 70%/2.6 mg, respectively, with or without 50 mg/kg/12 h oral dosage for 7 wks) in vivo with no apparent toxicity.
A cell-permeable thienopyrrolopyridazinone that exhibits good aqueous solubility (29.6 µg/mL or 79.5 µM in PBS, pH 7.4) and acts as a potent allosteric PKM2 activator (AC50 = 92 nM; [PKM2] = 0.1 nM) by stabilizing PKM2 tetramer via stoichiometric interaction with FBP-bound PKM2 (2 activator/4 FBP/tetramer) in a similar manner as PKM2 Activator III (Cat. No. 504537). Reprorted to retard human lung carcinoma H1299 proliferation under hypoxia, but not normoxia, condition in cultures (doubling time = 50 and 35 h, respectively, with or without 30 µM TEPP-46; 1% O2) in vitro and impair H1299 tumorigenesis in mice (50 mg/kg/12 h p.o.) in vivo with no apparent toxicity.

Biochem/physiol Actions

Cell permeable: yes
Primary Target
PKM2
Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Use only fresh DMSO for reconstitution.

Other Notes

Anastasiou, D., et al. 2012. Nat. Chem. Biol.8, 839.

Jiang, J.K., et al. 2010. Bioorg. Med. Chem. Lett.20, 3387.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Storage Class Code

11 - Combustible Solids

WGK

WGK 3

Flash Point(F)

Not applicable

Flash Point(C)

Not applicable

Certificates of Analysis (COA)

Search for Certificates of Analysis (COA) by entering the products Lot/Batch Number. Lot and Batch Numbers can be found on a product’s label following the words ‘Lot’ or ‘Batch’.

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