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Purity: ≥98%
| Targets |
CHMFL-PI3KD-317 targets phosphoinositide 3-kinase delta (PI3Kδ), a class I PI3K isoform that is predominantly expressed in leukocytes and plays a critical role in B-cell receptor signaling, T-cell activation, and immune cell function. It is a highly selective inhibitor with an IC50 of 6 nM for PI3Kδ. The compound exhibits over 10-1500 fold selectivity over other class I PI3K isoforms.
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| ln Vitro |
CHMFL-PI3KD-317 possesses anti-proliferative effects with GI50 of 3.5 ± 0.8, 4.0 ± 0.9, 4.8 ± 0.2, 3.3 ± 0.2, 3.0 ± compared to PF382, NALM-6, MV4-11, MOLM-14 and MOLM-13. 0.4 μM cells, in that order [1].
In vitro, CHMFL-PI3KD-317 inhibits PI3Kδ-mediated Akt T308 phosphorylation in Raji cells with an EC50 of 4.3 nM. The compound demonstrates potent antiproliferative effects on cancer cells. Its high selectivity for PI3Kδ over other PI3K isoforms (10-1500 fold) makes it a valuable tool for studying PI3Kδ-specific signaling pathways. |
| ln Vivo |
Mice's MOLM14 tumor growth is inhibited by CHMFL-PI3KD-317 (Compound 15i; 25, 50, and 100 mg/kg/day, orally, for 14 days) [1]. In Sprague-Dawley rats, CHMFL-PI3KD-317 has a respectable half-life (T1/2 = 3.28 h) and good oral bioavailability [1].
In vivo, CHMFL-PI3KD-317 has been evaluated in preclinical models of cancer and immune disorders. As an orally active PI3Kδ inhibitor, it has demonstrated efficacy in inhibiting tumor growth and modulating immune responses. The compound's high selectivity for PI3Kδ is expected to reduce off-target toxicities associated with pan-PI3K inhibitors. |
| Enzyme Assay |
In vitro enzyme assays for PI3Kδ inhibition involve incubating recombinant PI3Kδ enzyme with phosphatidylinositol-4,5-bisphosphate (PIP2) and ATP in the presence of varying concentrations of CHMFL-PI3KD-317. The production of phosphatidylinositol-3,4,5-trisphosphate (PIP3) is measured using radioactive or HTRF-based assays. IC50 values are calculated from dose-response curves to determine the compound's potency and selectivity over other PI3K isoforms.
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| Cell Assay |
Cellular assays are performed using Raji cells (B-cell lymphoma) or other hematopoietic cell lines. Cells are treated with CHMFL-PI3KD-317 at various concentrations. PI3Kδ pathway inhibition is assessed by measuring Akt phosphorylation at T308 by Western blot. Cell proliferation is measured by MTT or CellTiter-Glo assays to evaluate antiproliferative effects.
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| Animal Protocol |
Animal/Disease Models: Female nu/nu (nude) mice bearing MOLM-14 tumor xenografts [1]
Doses: 25, 50 and 100 mg/kg/day Route of Administration: Orally for 14 days Experimental Results: Inhibition of MOLM14 tumor growth, no deaths or significant weight loss in mice. In vivo studies are conducted in tumor-bearing mouse models, such as xenografts of Raji cells or other PI3Kδ-dependent tumors. CHMFL-PI3KD-317 is administered orally at various doses. Tumor volume is measured periodically, and tumors are harvested for biomarker analysis, including assessment of Akt phosphorylation and other downstream signaling markers by Western blot and immunohistochemistry. |
| ADME/Pharmacokinetics |
CHMFL-PI3KD-317 (molecular weight 494.03, formula C₂₁H₂₄ClN₅O₃S₂) is a small-molecule compound. It is orally active and soluble in DMSO. The compound is typically stored at -20°C. Its physicochemical properties support oral bioavailability and favorable drug-like characteristics.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies have evaluated CHMFL-PI3KD-317 in animal models. As a selective PI3Kδ inhibitor, its toxicity profile is related to immune modulation and potential effects on B-cell and T-cell function. The compound's high selectivity for PI3Kδ is expected to provide a favorable safety profile compared to pan-PI3K inhibitors.
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| References | |
| Additional Infomation |
CHMFL-PI3KD-317 is a highly potent and selective PI3Kδ inhibitor developed as a research tool and potential therapeutic agent. Its mechanism involves selective inhibition of PI3Kδ, blocking the PI3K/Akt/mTOR signaling pathway in immune cells. The compound exhibits over 10-1500 fold selectivity over other PI3K isoforms and has demonstrated antiproliferative effects on cancer cells. It is primarily used for research purposes.
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| Molecular Formula |
C21H24CLN5O3S2
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| Molecular Weight |
494.029960632324
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| Exact Mass |
493.1
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| CAS # |
2244992-76-3
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| PubChem CID |
137333450
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| Appearance |
White to off-white solid powder
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| LogP |
3.8
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
32
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| Complexity |
750
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1=C(C=C(C=N1)C1=C(C)N=C(NC([C@H](C(C)C)N)=O)S1)NS(C1C=CC=C(C)C=1)(=O)=O
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| InChi Key |
PIBKKQFQADCDAW-KRWDZBQOSA-N
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| InChi Code |
InChI=1S/C21H24ClN5O3S2/c1-11(2)17(23)20(28)26-21-25-13(4)18(31-21)14-9-16(19(22)24-10-14)27-32(29,30)15-7-5-6-12(3)8-15/h5-11,17,27H,23H2,1-4H3,(H,25,26,28)/t17-/m0/s1
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| Chemical Name |
(2S)-2-amino-N-[5-[6-chloro-5-[(3-methylphenyl)sulfonylamino]pyridin-3-yl]-4-methyl-1,3-thiazol-2-yl]-3-methylbutanamide
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| Synonyms |
CHMFL-PI3KD-317; CHMFL PI3KD-317; CHMFL-PI3KD 317
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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 |
| 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 : ~250 mg/mL (~506.04 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.21 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 20.8 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: ≥ 2.08 mg/mL (4.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0242 mL | 10.1208 mL | 20.2417 mL | |
| 5 mM | 0.4048 mL | 2.0242 mL | 4.0483 mL | |
| 10 mM | 0.2024 mL | 1.0121 mL | 2.0242 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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