PD-1-IN-1 (CA-170) (Synonyms: CA-170) |
| Catalog No.GC19225 |
PD-1-IN-1 (CA-170) es un inhibidor dual administrado por vÍa oral de VISTA y PD-L1.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1673534-76-3
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
PD-1-IN-1 (CA-170) is an orally active dual inhibitor of the immune checkpoint regulatory proteins VISTA and PD-L1[1]. PD-1-IN-1 (CA-170) does not directly bind to the target proteins; its mechanism of action might involve blocking their downstream signaling pathways[2]. PD-1-IN-1 (CA-170) exhibits anti-tumor activity similar to that of PD-1 monoclonal antibodies and offers advantages in terms of biosafety[3].
In vitro, PD-1-IN-1 (CA-170) (10-1000nM) treatment of human peripheral blood mononuclear cells (PBMCs) for 48h did not induce the secretion of cytokines IL-2, IFN-γ, and TNF-α, while anti-CD28 antibodies could induce this secretion [4].
In vivo, oral administration of PD-1-IN-1 (CA-170) (10 mg/kg) for 14 days inhibited tumor growth in a mouse model of colon cancer by 36%. However, it did not show significant efficacy in severely immunocompromised mice, demonstrating that the efficacy of PD-1-IN-1 (CA-170) relies on an immune-mediated mechanism[4]. In a mouse model of lung cancer, oral administration of PD-1-IN-1 (CA-170) (10 mg/kg) for 28 days reduced tumor burden by 63%, increased the number of intratumoral CD8+ T cells, and inhibited lung cancer metastasis[5].
References:
[1]Lazorchak A S, Patterson T, Ding Y, et al. Abstract A36: CA-170, an oral small molecule PD-L1 and VISTA immune checkpoint antagonist, promotes T cell immune activation and inhibits tumor growth in pre-clinical models of cancer[J]. Cancer Immunology Research, 2017, 5: A36-A36.
[2]Musielak B, Kocik J, Skalniak L, et al. CA-170–a potent small-molecule PD-L1 inhibitor or not?[J]. Molecules, 2019, 24(15): 2804.
[3]Wu Q, Jiang L, Li S, et al. Small molecule inhibitors targeting the PD-1/PD-L1 signaling pathway[J]. Acta Pharmacologica Sinica, 2021, 42(1): 1-9.
[4]Sasikumar P G, Sudarshan N S, Adurthi S, et al. PD-1 derived CA-170 is an oral immune checkpoint inhibitor that exhibits preclinical anti-tumor efficacy[J]. Communications biology, 2021, 4(1): 699.
[5]Pan J, Chen Y, Zhang Q, et al. Inhibition of lung tumorigenesis by a small molecule CA170 targeting the immune checkpoint protein VISTA[J]. Communications biology, 2021, 4(1): 906.
Cell experiment [1]: | |
Cell lines | Human PBMCs |
Preparation method | Human PBMCs from healthy donors were pre-cultured at high density (1×107 cells/ml) for 48 h to increase cell–cell contacts and immune scanning. The cells were then harvested and treated with anti-CD3 or anti-CD3 + anti-CD28 antibodies as positive controls, and PD-1-IN-1 (CA-170) (10 nM to 1000 nM). Release of IL-2, IFN-γ, and TNF-α was measured in the culture supernatants at 48 h. |
Reaction Conditions | 10-1000 nM ; 48 h |
Applications | In human PBMCs, CA-170 did not induce significant IL-2, IFN-γ, and TNF-α levels in both normal culture conditions or high-density culture conditions, while an antibody against CD28 induced as expected. |
Animal experiment [2]: | |
Animal models | Female A/J mice |
Preparation method | Mice were divided into five groups: (a) control mice that received PBS; (b) adjuvant control mice that received a STING agonist plusAddaVax; (c) KVax mice treated with KVax plus adjuvant; (d) PD-1-IN-1 (CA-170) treatment (10 mg/kg in PBS,) by oral gavage five times per week; (e) combined treatment with KVax/adjuvant plus PD-1-IN-1 (CA-170). Mice were administered one dose of the carcinogen vinyl carbamate31 (VC) by i.p. injection (16 mg/kg in sterile saline). PD-1-IN-1 (CA-170) treatment was started one week after VC induction of lung adenocarcinoma. |
Dosage form | 10 mg/kg; p.o. |
Applications | PD-1-IN-1 (CA-170) treatment decreased tumor load by 63% relative to the adjuvant control group. |
References: | |
| Cas No. | 1673534-76-3 | SDF | |
| Sinónimos | CA-170 | ||
| Canonical SMILES | C[C@@H](O)[C@@H](C(O)=O)NC(N[C@H](C1=NC([C@@H](N)CO)=NO1)CC(N)=O)=O | ||
| Formula | C12H20N6O7 | M.Wt | 360.32 |
| Solubility | DMSO : 28.5 mg/mL (79.10 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.7753 mL | 13.8766 mL | 27.7531 mL |
| 5 mM | 0.5551 mL | 2.7753 mL | 5.5506 mL |
| 10 mM | 0.2775 mL | 1.3877 mL | 2.7753 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 11 reference(s) in Google Scholar.)
GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.
Required fields are marked with *