5.33514

GADD45b/MKK7 Inhibitor, DTP3

• 동의어(들): GADD45b/MKK7 Inhibitor, DTP3, (R)-2-((R)-2-acetamido-3-(4-hydroxyphenyl)propanamido)-N-((R)-1-amino-1-oxo-3-phenylpropan-2-yl)-5-guanidinopentanamide trifluoroacetate, GADD45b-MKK blocker
• 실험식(Hill 표기법): C₂₆H₃₅N₇O₅ · xC₂HF₃O₂
• Molecular Weight: 525.60 (free base basis)
• UNSPSC 코드: 12352200
• PubChem Substance ID: 86295191
• NACRES: NA.77

속성

• 분석: ≥98% (HPLC)
• Quality Level: 100
• 양식: solid
• 효능: 65 nM K_i
• 제조업체/상표: Calbiochem^®
• 저장 조건: OK to freeze; desiccated (hygroscopic); protect from light
• 색상: white
• solubility: DMSO: 100 mg/mL; water: 100 mg/mL
• 저장 온도: 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
• InChI key: AOUZPXZGMZUQQS-UHFFFAOYSA-N

설명

일반 설명

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.

생화학적/생리학적 작용

Cell permeable: yes

Primary Target
GADD45b/MKK7

Reversible: yes

포장

Packaged under inert gas

경고

Toxicity: Standard Handling (A)

서열

Ac-YRF-NH2

물리적 형태

Supplied as a HCl salt.

재구성

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

기타 정보

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

법적 정보

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

안전성 정보

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point (°F): Not applicable
• Flash Point (°C): Not applicable