CA-170 free base | CAS#1673534-76-3 | PD-1 inhibitor

MedKoo Cat#: 206957 | Name: CA-170 free base

Description:

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

CA-170, also known as AUPM170 and PD-1-IN-17, is a programmed cell death-1 (PD-1) inhibitor. PD-1-IN-17 was first reported in patent WO2015033301A1, (Compound 4), inhibits 92% splenocyte proliferation at 100 nM.

Chemical Structure

CA-170 free base

CAS#1673560-66-1 (free base)

Theoretical Analysis

MedKoo Cat#: 206957

Name: CA-170 free base

CAS#: 1673560-66-1 (free base)

Chemical Formula: C13H22N6O7

Exact Mass: 374.1550

Molecular Weight: 374.35

Elemental Analysis: C, 41.71; H, 5.92; N, 22.45; O, 29.92

Price and Availability

Size	Price	Availability
50mg	USD 750.00	2 Weeks
100mg	USD 1,350.00	2 Weeks
200mg	USD 2,350.00	2 Weeks
500mg	USD 5,350.00	2 Weeks
1g	USD 8,450.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

1673560-66-1 (free base) 1673534-76-3 (PD-1-IN-1) CA-170 TFA

Synonym

PD-1-IN-17 free base; PD-1-IN17; CA-170; CA-170; CA-170; AUPM 170; AUPM-170; AUPM170; PD-L1/PD-L2/VISTA antagonist;

IUPAC/Chemical Name

L-Serine, N-[[[(1S)-4-amino-1-[5-[(1S,2R)-1-amino-2-hydroxypropyl]-1,3,4-oxadiazol-2-yl]-4-oxobutyl]amino]carbonyl]-

InChi Key

SRNQPYBWRIETFQ-XKBZYTNZSA-N

InChi Code

InChI=1S/C13H22N6O7/c1-5(21)9(15)11-19-18-10(26-11)6(2-3-8(14)22)16-13(25)17-7(4-20)12(23)24/h5-7,9,20-21H,2-4,15H2,1H3,(H2,14,22)(H,23,24)(H2,16,17,25)/t5-,6+,7+,9+/m1/s1

SMILES Code

OC[C@@H](C(O)=O)NC(N[C@H](C1=NN=C([C@@H](N)[C@H](O)C)O1)CCC(N)=O)=O

Appearance

Solid powder

Purity

>95% (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

>2 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

PD-1-IN-17 may be related to CA-170. The chemical structure of CA170 has not been disclosed as of 11/11/2019. CA-170, also known as AUPM 170, is an orally bioavailable small molecule inhibitor of the immune checkpoint regulatory proteins programmed cell death ligand-1 (PD-L1; B7-H1; CD274), PD-L2, and V-domain immunoglobulin (Ig) suppressor of T-cell activation (VISTA; programmed death 1 homolog; PD1H; PD-1H), with potential negative immune checkpoint regulatory and antineoplastic activities. CA-170 targets and binds to PD-L1, PD-L2 and VISTA. This inhibits PD-L1/PD-L2/VISTA-mediated signaling, abrogates the PD-L1-, PD-L2- and VISTA-induced suppression of T-lymphocyte immune responses, enhances cytotoxic T-cell proliferation and activation against tumor cells, increases cytokine production by T-cells, and inhibits tumor cell growth. PD-L1, PD-L2 and VISTA, negative checkpoint molecules of immune activation, play key roles in the suppression of T-cell functions. CA-170 that selectively targets PD-L1 and VISTA, both of which function as negative checkpoint regulators of immune activation. CA-170 can induce effective proliferation and IFN-γ (Interferon-gamma) production (a cytokine that is produced by activated T cells and is a marker of T cell activation) by T cells that are specifically suppressed by PD-L1 or VISTA. In addition, CA-170 also appears to have anti-tumor effects similar to anti-PD-1 or anti-VISTA antibodies in multiple in vivo tumor models. Curis is currently investigating CA-170 in a Phase 1 trial in patients with advanced solid tumors and lymphomas.

Product Data

Product Data

Instruction

View handling instruction

Biological target:

PD-1-IN-17 is a programmed cell death-1 (PD-1) inhibitor.

In vitro activity:

Flow cytometry and single-cell RNA sequencing (scRNA-seq) revealed that CA170 increased CD8+ T cell infiltration and enhanced their effector functions by decreasing the tumor infiltration of myeloid-derived suppressor cells (MDSCs) and Regulatory T (Treg) cells, while the Kras vaccine primarily induced expansion of CD4+ effector T cells. VISTA antagonism by CA170 revealed strong efficacy against lung tumorigenesis with broad immunoregulatory functions that influence effector, memory and regulatory T cells, and drives an adaptive T cell tumor-specific immune response that enhances the efficacy of the KRAS vaccine. Reference: Commun Biol. 2021 Jul 23;4(1):906. https://pubmed.ncbi.nlm.nih.gov/34302042/

In vivo activity:

The efficacy of CA-170 was explored using three independent immunocompetent tumor models established in mice: the CT26 and MC38 colon carcinoma model and the B16F10 melanoma lung metastasis model. As a single agent CA-170 dosed orally once a day showed a significant tumor growth inhibition in MC38 (43%; Fig. 5a) and significant reduction in metastatic counts in B16F10 (73%; Fig. 5b) models, respectively. In the CT26 colon carcinoma model, CA-170 showed an enhanced tumor growth inhibition in combination with docetaxel (68% TGI, p < 0.05; Fig. 5c) which is higher than TGI observed with docetaxel alone (43% TGI, p < 0.05; Fig. 5c). Reference: Commun Biol. 2021 Jun 8;4(1):699. https://pubmed.ncbi.nlm.nih.gov/34103659/

	Solvent	mg/mL	mM
Solubility
	DMSO	125.0	333.91
	Water	100.0	267.13

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 374.35 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.

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. Pan J, Chen Y, Zhang Q, Khatun A, Palen K, Xin G, Wang L, Yang C, Johnson BD, Myers CR, Sei S, Shoemaker RH, Lubet RA, Wang Y, Cui W, You M. Inhibition of lung tumorigenesis by a small molecule CA170 targeting the immune checkpoint protein VISTA. Commun Biol. 2021 Jul 23;4(1):906. doi: 10.1038/s42003-021-02381-x. PMID: 34302042; PMCID: PMC8302676. 2. Sasikumar PG, Sudarshan NS, Adurthi S, Ramachandra RK, Samiulla DS, Lakshminarasimhan A, Ramanathan A, Chandrasekhar T, Dhudashiya AA, Talapati SR, Gowda N, Palakolanu S, Mani J, Srinivasrao B, Joseph D, Kumar N, Nair R, Atreya HS, Gowda N, Ramachandra M. PD-1 derived CA-170 is an oral immune checkpoint inhibitor that exhibits preclinical anti-tumor efficacy. Commun Biol. 2021 Jun 8;4(1):699. doi: 10.1038/s42003-021-02191-1. PMID: 34103659; PMCID: PMC8187357.

In vitro protocol:

In vivo protocol:

1: Musielak B, Kocik J, Skalniak L, Magiera-Mularz K, Sala D, Czub M, Stec M, Siedlar M, Holak TA, Plewka J. CA-170 - A Potent Small-Molecule PD-L1 Inhibitor or Not? Molecules. 2019 Aug 1;24(15). pii: E2804. doi: 10.3390/molecules24152804. PubMed PMID: 31374878; PubMed Central PMCID: PMC6695792. 2: Shaabani S, Huizinga HPS, Butera R, Kouchi A, Guzik K, Magiera-Mularz K, Holak TA, Dömling A. A patent review on PD-1/PD-L1 antagonists: small molecules, peptides, and macrocycles (2015-2018). Expert Opin Ther Pat. 2018 Sep;28(9):665-678. doi: 10.1080/13543776.2018.1512706. Epub 2018 Sep 10. Review. PubMed PMID: 30107136; PubMed Central PMCID: PMC6323140. 3: Bojadzic D, Buchwald P. Toward Small-Molecule Inhibition of Protein-Protein Interactions: General Aspects and Recent Progress in Targeting Costimulatory and Coinhibitory (Immune Checkpoint) Interactions. Curr Top Med Chem. 2018;18(8):674-699. doi: 10.2174/1568026618666180531092503. Review. PubMed PMID: 29848279; PubMed Central PMCID: PMC6067980.