Talabostat mesylate
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MedKoo CAT#: 202730

CAS#: 150080-09-4 (mesylate)

Description: Talabostat, also known as PT-100 and BXCL701, is dipeptidyl peptidase inhibitor with antineoplastic and hematopoiesis- stimulating activities. By cleaving N-terminal Xaa-Pro or Xaa-Ala residues, talabostat inhibits dipeptidyl peptidases, such as fibroblast activation protein (FAP), resulting in the stimulation of cytokine and chemokine production and specific T-cell immunity and T-cell- dependent activity. This agent may also stimulate the production of colony stimulating factors, such as granulocyte colony stimulating factor (G-CSF), resulting in the stimulation of hematopoiesis. Dipeptidyl peptidases are involved in the activation of polypeptide hormones and chemokines.


Chemical Structure

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Talabostat mesylate
CAS# 150080-09-4 (mesylate)

Theoretical Analysis

MedKoo Cat#: 202730
Name: Talabostat mesylate
CAS#: 150080-09-4 (mesylate)
Chemical Formula: C10H23BN2O6S
Exact Mass: 214.15
Molecular Weight: 310.170
Elemental Analysis: C, 50.50; H, 8.95; B, 5.05; N, 13.09; O, 22.42

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1250 Ready to ship
500mg USD 2650 Ready to ship
1g USD 3750 Ready to ship
2g USD 6450 Ready to ship
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Related CAS #: 150080-09-4 (mesylate)   149682-77-9 (free base)  

Synonym: BXCL701; BXCL 701; BXCL-701; PT-100, PT100, PT 100, D05989, Val-boro-pro, Talabostat

IUPAC/Chemical Name: (R)-1-((S)-2-amino-3-methylbutanoyl)pyrrolidin-2-ylboronic acid methanesulfonic acid (1:1)

InChi Key: OXYYOEIGQRXGPI-WSZWBAFRSA-N

InChi Code: InChI=1S/C9H19BN2O3.CH4O3S/c1-6(2)8(11)9(13)12-5-3-4-7(12)10(14)15;1-5(2,3)4/h6-8,14-15H,3-5,11H2,1-2H3;1H3,(H,2,3,4)/t7-,8-;/m0./s1

SMILES Code: OB([C@H]1N(C([C@@H](N)C(C)C)=O)CCC1)O.CS(=O)(O)=O

Appearance: 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: >5 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: Talabostat (Val-boroPro, PT-100) is a dipeptidyl peptidase inhibitor with IC50 values of <4 nM, 4 nM, 11 nM, 310 nM, 560 nM and 390 nM for DPP-IV, DPP8, DPP9, QPP, FAP and PEP respectively.
In vitro activity: The inhibition of DPP8/9 by PT-100 results in the conversion of pro-caspase-1 into an activated form of pro-caspase-1, which then induces pyroptosis in monocytes and macrophages and stimulates the immune system (Fig. 6c). The absolute dependence on caspase-1, as demonstrated by the results in caspase-1 knockout cells and mice, is in itself sufficient to establish the cytotoxic effects as pyroptosis. However, it’s also shown that several other hallmarks of pyroptosis are present. These include: 1) the cleavage of GSDMD, the key effector of pyroptosis; 2) that knockout of GSDMD delays the cytotoxic response; 3) that the apoptotic caspases-3 and -7 and the apoptotic caspase substrate PARP are not cleaved; and 4) that the cell death appears lytic and not apoptotic by microscopy. Significantly, Val-boroPro’s cytotoxic effects appear to be completely selective to monocytes and macrophages. Reference: Nat Chem Biol. 2017 Jan;13(1):46-53. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477230/
In vivo activity: Oral administration of PT-100 to mice slowed growth of syngeneic tumors derived from fibrosarcoma, lymphoma, melanoma, and mastocytoma cell lines. In WEHI 164 fibrosarcoma and EL4 and A20/2J lymphoma models, PT-100 caused regression and rejection of tumors. The antitumor effect appeared to involve tumor-specific CTL and protective immunological memory. PT-100 treatment of WEHI 164-inoculated mice increased mRNA expression of cytokines and chemokines known to promote T-cell priming and chemoattraction of T cells and innate effector cells. The role of innate activity was further implicated by observation of significant, although reduced, inhibition of WEHI 164 and A20/2J tumors in immunodeficient mice. PT-100 also demonstrated ability to augment antitumor activity of rituximab and trastuzumab in xenograft models of human CD20(+) B-cell lymphoma and HER-2(+) colon carcinoma where antibody-dependent cytotoxicity can be mediated by innate effector cells responsive to the cytokines and chemokines up-regulated by PT-100. Although CD26/DPP-IV is a potential target for PT-100 in the immune system, it appeared not to be involved because antitumor activity and stimulation of cytokine and chemokine production was undiminished in CD26(-/-) mice. Reference: Cancer Res. 2004 Aug 1;64(15):5471-80. https://cancerres.aacrjournals.org/content/64/15/5471.long

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 62.0 199.88
Water 62.0 199.88
Ethanol 62.0 199.88

Preparing Stock Solutions

The following data is based on the product molecular weight 310.17 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. Okondo MC, Johnson DC, Sridharan R, Go EB, Chui AJ, Wang MS, Poplawski SE, Wu W, Liu Y, Lai JH, Sanford DG, Arciprete MO, Golub TR, Bachovchin WW, Bachovchin DA. DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis. Nat Chem Biol. 2017 Jan;13(1):46-53. doi: 10.1038/nchembio.2229. Epub 2016 Nov 7. PMID: 27820798; PMCID: PMC5477230. 2. Adams S, Miller GT, Jesson MI, Watanabe T, Jones B, Wallner BP. PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism. Cancer Res. 2004 Aug 1;64(15):5471-80. doi: 10.1158/0008-5472.CAN-04-0447. PMID: 15289357.
In vitro protocol: 1. Okondo MC, Johnson DC, Sridharan R, Go EB, Chui AJ, Wang MS, Poplawski SE, Wu W, Liu Y, Lai JH, Sanford DG, Arciprete MO, Golub TR, Bachovchin WW, Bachovchin DA. DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis. Nat Chem Biol. 2017 Jan;13(1):46-53. doi: 10.1038/nchembio.2229. Epub 2016 Nov 7. PMID: 27820798; PMCID: PMC5477230.
In vivo protocol: 1. Okondo MC, Johnson DC, Sridharan R, Go EB, Chui AJ, Wang MS, Poplawski SE, Wu W, Liu Y, Lai JH, Sanford DG, Arciprete MO, Golub TR, Bachovchin WW, Bachovchin DA. DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis. Nat Chem Biol. 2017 Jan;13(1):46-53. doi: 10.1038/nchembio.2229. Epub 2016 Nov 7. PMID: 27820798; PMCID: PMC5477230. 2. Adams S, Miller GT, Jesson MI, Watanabe T, Jones B, Wallner BP. PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism. Cancer Res. 2004 Aug 1;64(15):5471-80. doi: 10.1158/0008-5472.CAN-04-0447. PMID: 15289357.

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 1: Huang Y, Simms AE, Mazur A, Wang S, León NR, Jones B, Aziz N, Kelly T. Fibroblast activation protein-α promotes tumor growth and invasion of breast cancer cells through non-enzymatic functions. Clin Exp Metastasis. 2011 Aug;28(6):567-79. doi: 10.1007/s10585-011-9392-x. Epub 2011 May 22. PubMed PMID: 21604185.

2: Meany H, Balis FM, Aikin A, Whitcomb P, Murphy RF, Steinberg SM, Widemann BC, Fox E. Pediatric phase I trial design using maximum target inhibition as the primary endpoint. J Natl Cancer Inst. 2010 Jun 16;102(12):909-12. Epub 2010 May 11. PubMed PMID: 20460632; PubMed Central PMCID: PMC2886096.

3: Eager RM, Cunningham CC, Senzer NN, Stephenson J Jr, Anthony SP, O'Day SJ, Frenette G, Pavlick AC, Jones B, Uprichard M, Nemunaitis J. Phase II assessment of talabostat and cisplatin in second-line stage IV melanoma. BMC Cancer. 2009 Jul 30;9:263. PubMed PMID: 19643020; PubMed Central PMCID: PMC2731782.

4: Eager RM, Cunningham CC, Senzer N, Richards DA, Raju RN, Jones B, Uprichard M, Nemunaitis J. Phase II trial of talabostat and docetaxel in advanced non-small cell lung cancer. Clin Oncol (R Coll Radiol). 2009 Aug;21(6):464-72. Epub 2009 Jun 5. PubMed PMID: 19501491.

5: Pennisi A, Li X, Ling W, Khan S, Gaddy D, Suva LJ, Barlogie B, Shaughnessy JD, Aziz N, Yaccoby S. Inhibitor of DASH proteases affects expression of adhesion molecules in osteoclasts and reduces myeloma growth and bone disease. Br J Haematol. 2009 Jun;145(6):775-87. Epub 2009 Apr 8. PubMed PMID: 19388929; PubMed Central PMCID: PMC2748971.

6: Cristillo AD, Galmin L, Restrepo S, Hudacik L, Suschak J, Lewis B, Draghia-Akli R, Aziz N, Weiss D, Markham P, Pal R. HIV-1 Env vaccine comprised of electroporated DNA and protein co-administered with Talabostat. Biochem Biophys Res Commun. 2008 May 23;370(1):22-6. Epub 2008 Mar 7. PubMed PMID: 18329382.

7: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2007 Dec;29(10):697-735. PubMed PMID: 18200333.

8: Narra K, Mullins SR, Lee HO, Strzemkowski-Brun B, Magalong K, Christiansen VJ, McKee PA, Egleston B, Cohen SJ, Weiner LM, Meropol NJ, Cheng JD. Phase II trial of single agent Val-boroPro (Talabostat) inhibiting Fibroblast Activation Protein in patients with metastatic colorectal cancer. Cancer Biol Ther. 2007 Nov;6(11):1691-9. Epub 2007 Aug 14. PubMed PMID: 18032930.

9: Cunningham CC. Talabostat. Expert Opin Investig Drugs. 2007 Sep;16(9):1459-65. Review. PubMed PMID: 17714031.

10: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2006 Dec;28(10):719-40. PubMed PMID: 17235418.

11: Molecule of the month. Talabostat. Drug News Perspect. 2006 Jun;19(5):299. PubMed PMID: 16941051.