Numidargistat

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 206991

CAS#: 2095732-06-0

Description: Numidargistat, also known as INCB01158 and CB1158, is a potent and orally active arginase inhibitor with IC50=89 nM) . CB-1158 blocked myeloid cell-mediated suppression of T cell proliferation in vitro and reduced tumor growth in multiple mouse models of cancer, as a single agent and in combination with checkpoint blockade, adoptive T cell therapy, adoptive NK cell therapy, and the chemotherapy agent gemcitabine. CB-1158 increased tumor-infiltrating CD8+ T cells and NK cells, inflammatory cytokines, and expression of interferon-inducible genes. CB-1158 may be potentially useful in renal cell cancer, breast cancer, non-small cell lung cancer, acute myeloid leukemia, and other tumor types where arginase-secreting MDSCs are known to play an immunosuppressive role. (see ADDITIONAL INFORMATION in this web page for CB-1158 structure confusion).

Chemical Structure

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Numidargistat
CAS# 2095732-06-0
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 206991
Name: Numidargistat
CAS#: 2095732-06-0
Chemical Formula: C11H22BN3O5
Exact Mass: 287.17
Molecular Weight: 287.123
Elemental Analysis: C, 46.02; H, 7.72; B, 3.76; N, 14.64; O, 27.86

Price and Availability

This product is not in stock, which may be available by custom synthesis. For cost-effective reason, minimum order is 1g (price is usually high, lead time is 2~3 months, depending on the technical challenge). Quote less than 1g will not be provided. To request quote, please email to sales @medkoo.com or click below button.
Note: Price will be listed if it is available in the future.

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Related CAS #: 2095732-06-0   1345810-21-0    

Synonym: CB-1158; CB1158; CB 1158; INCB01158; INCB 01158; INCB-01158; INCB 001158; INCB-001158; INCB001158; Numidargistat;

IUPAC/Chemical Name: (3R,4S)-1-(L-alanyl)-3-amino-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid

InChi Key: ZZJLMZYUGLJBSO-LAEOZQHASA-N

InChi Code: InChI=1S/C11H22BN3O5/c1-7(13)9(16)15-5-8(3-2-4-12(19)20)11(14,6-15)10(17)18/h7-8,19-20H,2-6,13-14H2,1H3,(H,17,18)/t7-,8-,11-/m0/s1

SMILES Code: O=C([C@]1(N)CN(C([C@H](C)N)=O)C[C@@H]1CCCB(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

Shelf Life: >3 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: Note: Currently there are two versions of CB-1158, which have different chemical structure and CAS#. 1. The first version is CAS#1345810-21-0 Smile code: ClC1=CC(Cl)=CC=C1CN2CCC(C(N)(CCCCB(O)O)C(O)=O)CC2 We listed this structure as CB1158. The structure can be found in below resources: (1). Current Opinion in Pharmaology 2017, 35. 30-39 (2). Pham et al . Drug Discov Today. 2018. Apr;23(4):871-878. (3). The CB1158 structure is further confirmed by Scifinder database, in which CB1158 has CAS#1345810-21-0 2. The second version is CAS#2095732-06-0 Smile code: O=C([C@]1(N)CN(C([C@H](C)N)=O)C[C@@H]1CCCB(O)O)O This structure can be found in below resource: https://chem.nlm.nih.gov/chemidplus/name/cb-1158 We keep post if we can confirm CB-1158 structure from authoritative resources.

Product Data:
Product Data
Certificate of Analysis:
View CoA: current batch, Lot# A22O01B20
Safety Data Sheet (SDS):
View Safety Data Sheet (SDS)
Instruction:
View handling instruction
Biological target: Numidargistat (CB-1158) is a potent and orally active inhibitor of arginase, with IC50s of 86 nM and 296 nM.
In vitro activity: CB-1158 blocked myeloid cell-mediated suppression of T cell proliferation in vitro and reduced tumor growth in multiple mouse models of cancer, as a single agent and in combination with checkpoint blockade, adoptive T cell therapy, adoptive NK cell therapy, and the chemotherapy agent gemcitabine. Profiling of the tumor microenvironment revealed that CB-1158 increased tumor-infiltrating CD8+ T cells and NK cells, inflammatory cytokines, and expression of interferon-inducible genes. Reference: J Immunother Cancer. 2017 Dec 19;5(1):101. https://pubmed.ncbi.nlm.nih.gov/29254508/
In vivo activity: Immunosuppressive macrophages are classically defined by expression of the enzyme Arginase 1 (Arg1), which this study demonstrated is potently expressed in pancreatic tumor associated macrophages from both human patients and mouse models. Genetic inactivation of Arg1 in macrophages, using a dual recombinase genetically engineered mouse model of pancreatic cancer, delayed formation of invasive disease, while increasing CD8+ T cell infiltration. Treatment of established tumors with the arginase inhibitor CB-1158 exhibited further increased CD8+ T cell infiltration, beyond that seen with the macrophage-specific knockout, and sensitized the tumors to anti-PD1 immune checkpoint blockade. Reference: Elife. 2023 Feb 2;12:e80721. https://pubmed.ncbi.nlm.nih.gov/36727849/

Preparing Stock Solutions

The following data is based on the product molecular weight 287.12 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. Grobben Y, Uitdehaag JCM, Willemsen-Seegers N, Tabak WWA, de Man J, Buijsman RC, Zaman GJR. Structural insights into human Arginase-1 pH dependence and its inhibition by the small molecule inhibitor CB-1158. J Struct Biol X. 2019 Nov 26;4:100014. doi: 10.1016/j.yjsbx.2019.100014. PMID: 32647818; PMCID: PMC7337048. 2. Steggerda SM, Bennett MK, Chen J, Emberley E, Huang T, Janes JR, Li W, MacKinnon AL, Makkouk A, Marguier G, Murray PJ, Neou S, Pan A, Parlati F, Rodriguez MLM, Van de Velde LA, Wang T, Works M, Zhang J, Zhang W, Gross MI. Inhibition of arginase by CB-1158 blocks myeloid cell-mediated immune suppression in the tumor microenvironment. J Immunother Cancer. 2017 Dec 19;5(1):101. doi: 10.1186/s40425-017-0308-4. PMID: 29254508; PMCID: PMC5735564. 3. Menjivar RE, Nwosu ZC, Du W, Donahue KL, Hong HS, Espinoza C, Brown K, Velez-Delgado A, Yan W, Lima F, Bischoff A, Kadiyala P, Salas-Escabillas D, Crawford HC, Bednar F, Carpenter E, Zhang Y, Halbrook CJ, Lyssiotis CA, Pasca di Magliano M. Arginase 1 is a key driver of immune suppression in pancreatic cancer. Elife. 2023 Feb 2;12:e80721. doi: 10.7554/eLife.80721. Epub ahead of print. PMID: 36727849.
In vitro protocol: 1. Grobben Y, Uitdehaag JCM, Willemsen-Seegers N, Tabak WWA, de Man J, Buijsman RC, Zaman GJR. Structural insights into human Arginase-1 pH dependence and its inhibition by the small molecule inhibitor CB-1158. J Struct Biol X. 2019 Nov 26;4:100014. doi: 10.1016/j.yjsbx.2019.100014. PMID: 32647818; PMCID: PMC7337048. 2. Steggerda SM, Bennett MK, Chen J, Emberley E, Huang T, Janes JR, Li W, MacKinnon AL, Makkouk A, Marguier G, Murray PJ, Neou S, Pan A, Parlati F, Rodriguez MLM, Van de Velde LA, Wang T, Works M, Zhang J, Zhang W, Gross MI. Inhibition of arginase by CB-1158 blocks myeloid cell-mediated immune suppression in the tumor microenvironment. J Immunother Cancer. 2017 Dec 19;5(1):101. doi: 10.1186/s40425-017-0308-4. PMID: 29254508; PMCID: PMC5735564.
In vivo protocol: 1. Menjivar RE, Nwosu ZC, Du W, Donahue KL, Hong HS, Espinoza C, Brown K, Velez-Delgado A, Yan W, Lima F, Bischoff A, Kadiyala P, Salas-Escabillas D, Crawford HC, Bednar F, Carpenter E, Zhang Y, Halbrook CJ, Lyssiotis CA, Pasca di Magliano M. Arginase 1 is a key driver of immune suppression in pancreatic cancer. Elife. 2023 Feb 2;12:e80721. doi: 10.7554/eLife.80721. Epub ahead of print. PMID: 36727849.

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1: Steggerda SM, Bennett MK, Chen J, Emberley E, Huang T, Janes JR, Li W, MacKinnon AL, Makkouk A, Marguier G, Murray PJ, Neou S, Pan A, Parlati F, Rodriguez MLM, Van de Velde LA, Wang T, Works M, Zhang J, Zhang W, Gross MI. Inhibition of arginase by CB-1158 blocks myeloid cell-mediated immune suppression in the tumor microenvironment. J Immunother Cancer. 2017 Dec 19;5(1):101. doi: 10.1186/s40425-017-0308-4. PubMed PMID: 29254508; PubMed Central PMCID: PMC5735564.