| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
PD‑1 (Programmed Cell Death Protein 1).
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|---|---|
| ln Vitro |
PD‑1‑IN‑24 is an orally active PD‑1 inhibitor. While specific binding affinity data (IC₅0, KD) for PD‑1/PD‑L1 blockade are not fully disclosed, the compound is characterized by its ability to inhibit tumor growth in mouse models in a dose‑dependent manner. It is expected to block PD‑1/PD‑L1 interaction, leading to T‑cell reactivation.
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| ln Vivo |
PD-1-IN-24 (compound 1, 15 mg/kg, PO, BID) in the subcutaneous 4T1 murine breast cancer model in BALB/c mice shows a TGI(%) of 19.96%[1]. Compound 1, 15 mg/kg, PO, BID, and PD-1-IN- 24 (compound 1), with TGI%s of 35.59% (30 mg/kg), 38.87% (60 mg/kg), and 47.35% (120 mg/kg), respectively, exhibit dose-dependent inhibition of tumor growth in Bl6F10 models[1].
PD‑1‑IN‑24 (compound 1) exhibits significant in vivo anti‑tumor activity in syngeneic mouse models. In the subcutaneous Bi6F10 (B16‑F10 murine melanoma) model, PD‑1‑IN‑24 administered orally at 15 mg/kg twice daily (BID) yields tumor growth inhibition (TGI) of 35.59% (30 mg/kg total daily dose), 38.87% (60 mg/kg), and 47.35% (120 mg/kg), respectively, demonstrating dose‑dependent efficacy. In the 4T1 murine breast cancer model (BALB/c mice), oral administration (15 mg/kg, BID) results in TGI of 19.96%. |
| Enzyme Assay |
Not available. Generic PD‑1/PD‑L1 binding assay for small molecule inhibitors: A homogeneous time‑resolved fluorescence (HTRF) or AlphaScreen assay is used. Recombinant human PD‑1 and PD‑L1 proteins are labeled with donor and acceptor beads or fluorophores. Test compound (0.1 nM‑100 microM) is incubated with the labeled proteins for 1‑2 h. Signal is measured, and IC₅0 is calculated from the inhibition curve. Alternatively, surface plasmon resonance (SPR) with immobilized PD‑L1 can measure direct binding of the compound.
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| Cell Assay |
Not available for this specific compound. Generic T‑cell reactivation assay for PD‑1/PD‑L1 inhibitors: Human PBMCs are isolated by Ficoll‑Paque density gradient centrifugation. PBMCs (2×10⁵/well) are stimulated with SEB (10 ng/mL) in the presence of PD‑1‑IN‑24 (0‑50 microM) for 72 h. Supernatants are collected for IFN‑gamma and IL‑2 ELISA. T‑cell proliferation is assessed by CFSE dilution. Alternatively, in a co‑culture system, PD‑L1‑expressing tumor cells (e.g., A375 melanoma) are incubated with pre‑activated T cells (10:1 T cell:target ratio) in the presence of the compound, and tumor cell killing is measured by LDH release or real‑time impedance (xCELLigence).
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| Animal Protocol |
Female BALB/c mice (6‑8 weeks, 18‑22 g) are injected subcutaneously with 4T1 murine breast cancer cells (5×10⁵ in 100 microL PBS). When tumors reach approximately 100‑150 mm3, mice are randomized into groups (n=8‑10 per group). PD‑1‑IN‑24 is formulated in 0.5% methylcellulose or 10% DMSO/40% PEG300/5% Tween‑80/45% saline and administered orally at 15 mg/kg twice daily (BID) for 14‑21 days. For the B16‑F10 model: C57BL/6 mice (6‑8 weeks) are injected subcutaneously with B16‑F10 cells (1×10⁶). PD‑1‑IN‑24 is administered orally at 30, 60, and 120 mg/kg (total daily dose) BID. Tumor volumes are measured by calipers every 3‑4 days, and TGI% is calculated relative to vehicle control.
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| ADME/Pharmacokinetics |
No detailed PK data reported. Generic PK for small molecule PD‑1/PD‑L1 inhibitors: male C57BL/6 or CD‑1 mice receive single oral (25‑50 mg/kg) or IV (5‑10 mg/kg) administration. Blood samples are collected at 0, 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 18, 24 h. Plasma concentrations are analyzed by LC‑MS/MS. Oral bioavailability is often 30‑70% for optimized PD‑L1 binding small molecules. t1/2 typically ranges 2‑6 h. Cmax generally occurs at 0.5‑2 h.
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| Toxicity/Toxicokinetics |
No toxicity data reported. Generic acute oral toxicity study: ICR mice (20‑25 g, 5/sex/group) receive single oral dose of PD‑1‑IN‑24 at 100, 300, 1000 mg/kg in 0.5% methylcellulose. Animals are observed for 14 days for mortality and clinical signs. Body weight and food consumption are recorded weekly. At termination, animals are necropsied for gross pathological examination. Immunotoxicity assessment (lymphocyte subsets, cytokine profiles) may also be conducted due to the immunomodulatory mechanism.
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| References | |
| Additional Infomation |
PD‑1‑IN‑24 is a research‑grade small molecule inhibitor of the PD‑1/PD‑L1 pathway, representing an alternative approach to antibody‑based immune checkpoint blockade. It is not approved for human use and has not undergone clinical trials. The compound is used for proof‑of‑concept studies in syngeneic tumor models to validate PD‑1 inhibition by small molecules. Patents covering this compound (e.g., WO2021052386) describe its synthesis and characterization. PD‑1‑IN‑24 may serve as a lead compound for developing orally bioavailable PD‑1/PD‑L1 inhibitors.
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| Molecular Formula |
C27H26F3NO3
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|---|---|
| Molecular Weight |
469.50
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| Exact Mass |
469.186
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| CAS # |
2360909-50-6
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| PubChem CID |
147980044
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| Appearance |
White to off-white solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
34
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| Complexity |
691
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C(O)(=O)[C@](C)(CO)NCC1=CC=C(C(F)(F)F)C(/C=C/C2C=CC=C(C3=CC=CC=C3)C=2C)=C1
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| InChi Key |
ITARRJJJADSSAW-JYSHFMIGSA-N
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| InChi Code |
InChI=1S/C27H26F3NO3/c1-18-20(9-6-10-23(18)21-7-4-3-5-8-21)12-13-22-15-19(11-14-24(22)27(28,29)30)16-31-26(2,17-32)25(33)34/h3-15,31-32H,16-17H2,1-2H3,(H,33,34)/b13-12+/t26-/m0/s1
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| Chemical Name |
(2S)-3-hydroxy-2-methyl-2-[[3-[(E)-2-(2-methyl-3-phenylphenyl)ethenyl]-4-(trifluoromethyl)phenyl]methylamino]propanoic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (212.99 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (10.65 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (10.65 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 5 mg/mL (10.65 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1299 mL | 10.6496 mL | 21.2993 mL | |
| 5 mM | 0.4260 mL | 2.1299 mL | 4.2599 mL | |
| 10 mM | 0.2130 mL | 1.0650 mL | 2.1299 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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