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531465 Val-boroPro - CAS 150080-09-4 - Calbiochem

An orally available, potent, reversible, and transition state analog inhibitor of DPP-IV (IC₅₀ = 26 nM)

Val-boroPro - CAS 150080-09-4 - Calbiochem : FDS (Fiches de données de sécurité), certificats d’analyse (CoA) et de qualité (CoQ), dossiers, brochures et autres documents disponibles.

Synonymes: H₂N-(S)-Val-(R)-boroPro-OH, CH₃SO₃H, H-(S)-Val-(R)-boroPro-OH, CH₃SO₃H, Valinyl-L-boroproline, CH₃SO₃H, DPP Inhibitor, PT-100, Talabostat

Primary Target: DPP-IV, DPP8 and DPP9
531465
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Aperçu

Replacement Information

Tableau de caractéristiques principal

CAS #Empirical Formula
150080-09-4C₁₀H₂₃BN₂O₆S

Products

RéférenceConditionnement Qté
5314650001 Flacon en verre 10 mg
Description
OverviewAn orally available amino boronic acid dipeptide with antihyperglycemic and anticancer properties. Acts as a highly potent, reversible, and transition state analog inhibitor of dipeptidyl peptidase IV (DPP-IV; IC50 = 26 nM; Ki = 180 pM). Also inhibits the activity of other prolyl peptidases (IC50 = 15 nM for DPP-II; and Ki = 1.5 nM and 760 pM for DPP8 and DPP9, respectively) and at much higher concentrations affects the activities of quiescent cell proline dipeptidase (QPP, DPP7; IC50 = 310 nM), PEP (IC50 = 390 nM) and fibroblast activation protein (FAP; IC50 = 560 nM). However, it does not inhibit the activity of trypsin, chymoptrypsin, thrombin, plasmin, tryptase, leukocyte elastase, and plasma kallikrein even at high levels (~100 µM). Promotes hematopoiesis and the growth of primitive hematopoietic progenitor cells by increasing the production of G-CSF, IL-6, and IL-11 by bone marrow stromal cells in mice. Although it has no direct cytotoxic effect on tumors in vitro, but oral administration in mice is shown to reduce the growth of syngeneic tumors derived from fibrosarcoma (WEHI164), lymphoma (EL4 and A20/2J), melanoma (B16-F10), and mastocytoma (P815) cell lines and augments antibody-dependent cell-mediated cytotoxicity. Note: In aqueous physiological solutions, it can cyclize in a time-dependent manner causing a 100-fold diminution in its inhibitory potency. However, at lower pH range it remains in an active open chain form. Maximum tolerated dose in mice or rats is ~ 25 µg/kg.

Please note that the molecular weight for this compound is batch-specific due to variable water content.
Catalogue Number531465
Brand Family Calbiochem®
SynonymsH₂N-(S)-Val-(R)-boroPro-OH, CH₃SO₃H, H-(S)-Val-(R)-boroPro-OH, CH₃SO₃H, Valinyl-L-boroproline, CH₃SO₃H, DPP Inhibitor, PT-100, Talabostat
References
ReferencesPoplawski, S.E., et al. 2011, J. Med. Chem. 54, 2022.
Connolly, B.A., et al. 2008. J. Med. Chem. 51, 6005.
Lankas, G.R., et al. 2005. Diabetes 54, 2988.
Cheng, J.D., et al. 2005. Mol. Cancer Ther. 4, 351.
Adams, S., et al. 2004. Cancer Res. 64, 5471.
Jones, B., et al. 2003. Blood 102, 1641.
Coutts, S.J., et al. 1996. J. Med. Chem. 39, 2087.
Snow, R.J., et al. 1994. J. Am. Chem. Soc. 116, 10860.
Kelly, T.A., et al. 1993. J. Am. Chem. Soc. 115, 12637.
Product Information
CAS number150080-09-4
FormLight beige solid
Hill FormulaC₁₀H₂₃BN₂O₆S
Chemical formulaC₁₀H₂₃BN₂O₆S
Hygroscopic Hygroscopic
ReversibleY
Quality LevelMQ100
Applications
Biological Information
Primary TargetDPP-IV, DPP8 and DPP9
Primary Target IC<sub>50</sub>15 nM for DPP-II
Primary Target K<sub>i</sub>180 pM
Secondary targetQPP, PEP and FAP
Purity≥98% by HPLC
Physicochemical Information
Cell permeableY
Dimensions
Materials Information
Toxicological Information
Safety Information according to GHS
Safety Information
Product Usage Statements
Storage and Shipping Information
Ship Code Ambient Temperature Only
Toxicity Standard Handling
Storage +2°C to +8°C
Protect from Light Protect from light
Hygroscopic Hygroscopic
Do not freeze Ok to freeze
Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Packaging Information
Packaged under inert gas Packaged under inert gas
Transport Information
Supplemental Information
Specifications
Global Trade Item Number
Référence GTIN
5314650001 04055977260328

Documentation

Val-boroPro - CAS 150080-09-4 - Calbiochem FDS

Titre

Fiche de données de sécurité des matériaux (FDS) 

Val-boroPro - CAS 150080-09-4 - Calbiochem Certificats d'analyse

TitreNuméro de lot
531465

Références bibliographiques

Aperçu de la référence bibliographique
Poplawski, S.E., et al. 2011, J. Med. Chem. 54, 2022.
Connolly, B.A., et al. 2008. J. Med. Chem. 51, 6005.
Lankas, G.R., et al. 2005. Diabetes 54, 2988.
Cheng, J.D., et al. 2005. Mol. Cancer Ther. 4, 351.
Adams, S., et al. 2004. Cancer Res. 64, 5471.
Jones, B., et al. 2003. Blood 102, 1641.
Coutts, S.J., et al. 1996. J. Med. Chem. 39, 2087.
Snow, R.J., et al. 1994. J. Am. Chem. Soc. 116, 10860.
Kelly, T.A., et al. 1993. J. Am. Chem. Soc. 115, 12637.
Fiche technique

Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.

Revision15-August-2014 JSW
SynonymsH₂N-(S)-Val-(R)-boroPro-OH, CH₃SO₃H, H-(S)-Val-(R)-boroPro-OH, CH₃SO₃H, Valinyl-L-boroproline, CH₃SO₃H, DPP Inhibitor, PT-100, Talabostat
DescriptionA prolineboronic acid-based broad-spectrum DDP IV activity and/or structural homologue (DASH) family dipeptidyl peptidases inhibitor that converts in solution between the protonated active form and a cyclized inactive form due to a reversible intramolecular B-N dative bond formation of the non-protonated Val-boroPro (kinact = 6.4 x 10--4 s- and kcyc = 6.4 x 10-5 s- at pH 7.8). Although equilibrium favors cyclization at basic pH, high affinity binding (kon & koff toward CD26 at pH 7.8 = 5.02 x 106 M-s- and 77.8 x 10-6 s-, respectively) drives the equilibrium away from cyclization and traps the active form in enzyme-bound state with prolonged incubation. Reported to inhibit DPP7/DPPII/QPP (IC50/[Substrate]/rxn time at pH 5.5 = 15 nM/500 µM Lys-Pro-MNA/1 h & 310 nM/50 µM Nle-Pro-AMC/15 min), CD26/DPPIV (IC50 = 26 nM; 500 µM Ala-Pro-MNA for 1 h at pH 7.8), fibroblast activation protein/FAP (IC50 = 40 nM; 250 µM Ala-Pro-AFC at pH 2.0), DPP8 (IC50 = 4 nM; 100 µM Ala-Pro-AFC for 15 min at pH 8.0), DDP9 (IC50 = 11 nM; 100 µM Gly-Pro-AMC for 30 min at pH 7.4) with little potency against 9 other proteases (IC50 >100 µM; aminopeptidase P, chymoptrypsin, leukocyte elastase, plasma kallikrein, plasmin, prolidase, thrombin, trypsin, tryptase), while contradictory reports regarding prolyl endopeptidase/PEP/PREP inhibition exist (e.g. IC50 = 390 nM/50 µM Z-Gly-Pro-AMC/pH 7.5/30 min vs. 25 µM/500 µM Z-Gly-Pro-MNA/pH 7.8/60 min). Shown to promote the propagation of human BM CD34+ cells by stimulating stromal cells cytokine production in vitro (min EC 0.1 nM) and display hematopoietic stimulatory effect in mice in vivo (min ED 2 µg/mouse/12 h; p.o.). Although orally available in mice and rats, caution must be taken not to exceed toxicity levels (MTD = 25 µg/mL using Sprague-Dawley rats; LD50 ~0.5 mg/mL in 24 survival test using Fisher rats; p.o.) for in vivo studies.
FormLight beige solid
Intert gas (Yes/No) Packaged under inert gas
CAS number150080-09-4
Chemical formulaC₁₀H₂₃BN₂O₆S
Purity≥98% by HPLC
SolubilityDMSO (100 mg/ml). Use only fresh DMSO for reconstitution.
Storage Protect from light
+2°C to +8°C
Hygroscopic
Do Not Freeze Ok to freeze
Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Toxicity Standard Handling
ReferencesPoplawski, S.E., et al. 2011, J. Med. Chem. 54, 2022.
Connolly, B.A., et al. 2008. J. Med. Chem. 51, 6005.
Lankas, G.R., et al. 2005. Diabetes 54, 2988.
Cheng, J.D., et al. 2005. Mol. Cancer Ther. 4, 351.
Adams, S., et al. 2004. Cancer Res. 64, 5471.
Jones, B., et al. 2003. Blood 102, 1641.
Coutts, S.J., et al. 1996. J. Med. Chem. 39, 2087.
Snow, R.J., et al. 1994. J. Am. Chem. Soc. 116, 10860.
Kelly, T.A., et al. 1993. J. Am. Chem. Soc. 115, 12637.