 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C27H27FN6O2 |
| Molecular Weight | 486.54 |
| Exact Mass | 486.22 |
| Elemental Analysis | C, 66.65; H, 5.59; F, 3.90; N, 17.27; O, 6.58 |
| Related CAS # | 2628486-22-4;NDI-101150 |
| Appearance | Typically exists as solids at room temperature |
| Density | 1.427±0.14 g/cm3 |
| LogP | 3.1 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 36 |
| Complexity | 787 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | C1(=O)C2=C(C(C3N4C(=NC=3)C=C(F)C=C4)=CC=C2NC2=NC(CN(C)C)=C([C@@H]3CCOC3)C=C2)CN1 |
| InChi Key | QOMXZMCZISKNPU-MRXNPFEDSA-N |
| InChi Code | InChI=1S/C27H27FN6O2/c1-33(2)14-22-18(16-8-10-36-15-16)4-6-24(32-22)31-21-5-3-19(20-12-30-27(35)26(20)21)23-13-29-25-11-17(28)7-9-34(23)25/h3-7,9,11,13,16H,8,10,12,14-15H2,1-2H3,(H,30,35)(H,31,32)/t16-/m1/s1 |
| Chemical Name | 1H-Isoindol-1-one, 7-[[6-[(dimethylamino)methyl]-5-[(3R)-tetrahydro-3-furanyl]-2-pyridinyl]amino]-4-(7-fluoroimidazo[1,2-a]pyridin-3-yl)-2,3-dihydro- (ACI) |
| Synonyms | NDI101150; NDI-101150; SCHEMBL23089119; BDBM500814; US11021481, Compound I-479; (S)-7-((6- ((dimethylamino)- methyl)-5- (tetrahydrofuran- 3-yl)pyridin- 2-yl)amino)-4- (7-fluoroimidazo [1,2-a]pyridin- 3-yl)isoindolin- 1-one; NDI-101150 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | HPK1 |
| ln Vitro | Hematopoietic progenitor kinase 1 (HPK1), a hematopoietic cell-restricted member of the serine/threonine Ste20-related protein kinases, is a negative regulator of the T cell receptor, B cell receptor, and dendritic cells. Loss of HPK1 kinase function increases cytokine secretion and enhances T cell signaling, virus clearance, and tumor growth inhibition. Therefore, HPK1 is considered a promising target for tumor immunotherapy. Several HPK1 inhibitors have been reported to regulate T cell function. In addition, HPK1-targeting PROTACs, which can induce the degradation of HPK1, have also been developed. Here, we provide an overview of research concerning HPK1 protein structure, function, and inhibitors and propose perspectives and insights for the future development of agents targeting HPK1[2]. |
| References |
[1]. Preparation of substituted pyrrolopyridinones as HPK1 antagonists and uses thereof. WO2021050964 A1, 2021-03-18. [2]. Hematopoietic Progenitor Kinase 1 in Tumor Immunology: A Medicinal Chemistry Perspective. J Med Chem. 2022 Jun 23;65(12):8065-8090. |
| Additional Infomation | The present invention provides compounds I [Z = CR or N; X = a covalent bond, O, S, C(O), etc.; R1 = (un)substituted alkyl, Ph, 3-7 membered saturated or partially unsaturated monocyclic carbocycyl, etc.; R2 = (un)substituted 6-11 membered saturated, partially unsaturated, or unsaturated fused, bridged, or spiro bicyclic ring having 0-3 heteroatoms independently selected from N, O, and S; R3 = H or alkyl; R = H, CN, halo, etc.; m = 0-2] or pharmaceutically acceptable salts thereof, compositions thereof, and methods of using the same for the inhibition of HPK1, and the treatment of HPK1-mediated disorders. E.g., a multi-step synthesis of II, starting from 5-bromo-2-chloronicotinic acid, was described. Exemplified compounds I were tested for HPK1 enzyme inhibition (data given). |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0553 mL | 10.2766 mL | 20.5533 mL | |
| 5 mM | 0.4111 mL | 2.0553 mL | 4.1107 mL | |
| 10 mM | 0.2055 mL | 1.0277 mL | 2.0553 mL |