GADD45B/MKK7 INHIBITOR DTP3 (C15-1305-132)

General description

A cell permeable, bioavailable D-tripeptide that specifically binds to MKK7 in 1:1 stoichiometry and disrupts the GADD45b/MKK7 complex in an allosteric mechanism (K_d = 65 nM, IC₅₀ = 160 pM). Does not affect the activity of 142 other protein kinases. Exhibits potent and selective activity in both multiple myeloma (MM) and non-MM cell lines expressing high levels of GADD45b, however, it is completely inactive in tumor cells featuring low GADDb expression. Displays potency similar to bortezomib, but has about 100-fold greater selectivity for cancer cells, and unlike bortezomib, it does not display any toxic effects in normal cell lines. Shown to activate JNK, but does not affect p38, ERK, or IKK/NF-κB signaling in sensitive GADD45b dependent MM cell lines. Abolishes the growth of myeloma xenografts in mice (14.5 mg/kg/day) and retains anticancer activity in an orthotopic xenograft model of MM. Displays desirable pharmacokinetic profile (t1/2 = 1.26 h and AUC = 6.43 mg/h/ml; at ~10 mg/kg, i.v).

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

A cell permeable, bioavailable D-tripeptide that specifically binds to MKK7 in 1:1 stoichiometry and disrupts the GADD45b/MKK7 complex in an allosteric mechanism (K_d = 65 nM, IC₅₀ = 160 pM). Does not affect the activity of 142 other protein kinases. Exhibits potent and selective activity in both multiple myeloma (MM) and non-MM cell lines expressing high levels of GADD45b, however, it is completely inactive in tumor cells featuring low GADDb expression. Displays potency similar to bortezomib, but has about 100-fold greater selectivity for cancer cells, and unlike bortezomib, it does not display any toxic effects in normal cell lines. Shown to activate JNK, but does not affect p38, ERK, or IKK/NF-κB signaling in sensitive GADD45b dependent MM cell lines. Abolishes the growth of myeloma xenografts in mice (14.5 mg/kg/day) and retains anticancer activity in an orthotopic xenograft model of MM. Displays desirable pharmacokinetic profile (t_1/2= 1.26 h and AUC = 6.43 mg/h/ml; at ~10 mg/kg, i.v).

Biochem/physiol Actions

Cell permeable: yes

Primary Target
GADD45b/MKK7

Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Sequence

Ac-YRF-NH2

Physical form

Supplied as a HCl salt.

Reconstitution

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

Other Notes

Tomatore, L., et al. 2014. Cancer Cell.26, 495.

Legal Information

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

Molecular Weight: 525.60 (free base basis). Empirical Formula: C₂₆H₃₅N₇O₅ · xC₂HF₃O₂. Assay: ≥. 98% (HPLC). Quality Level: 100. form: solid. potency: 65 . nM K_i. manufacturer/tradename: Calbiochem^®. . storage condition: OK to freeze, desiccated (hygroscopic), protect from light. color: white. solubility: DMSO: 100 . mg/mL, water: 100 . mg/mL. storage temp.: 2-8°C. SMILES string: CC(: O)NC(CC1: CC: C(C: C1)O)C(: O)NC(CCCN: C(N)N)C(: O)NC(CC2: CC: CC: C2)C(: O)N. Storage Class Code: 11 - Combustible Solids. WGK: WGK 3. Flash Point(F): Not applicable. Flash Point(C): Not applicable.