| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
(3S,4R)-GNE-6893 targets hematopoietic progenitor kinase 1 (HPK1, MAP4K1), a serine/threonine kinase that acts as a negative regulator of T cell activation. HPK1 phosphorylates SLP-76, leading to the recruitment of the adaptor protein Gads and the E3 ubiquitin ligase c-Cbl, which promotes the ubiquitination and degradation of signaling proteins, thereby dampening TCR signaling. By inhibiting HPK1, (3S,4R)-GNE-6893 relieves this negative regulation, enhancing T cell proliferation, cytokine production, and anti-tumor immunity. This makes HPK1 inhibition a promising strategy for cancer immunotherapy.
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| ln Vitro |
(3S,4R)-GNE-6893 is a potent and orally active HPK1 inhibitor. It can be used in research of cancer. No specific IC50 values for HPK1 inhibition are reported in the search results. As a potent inhibitor, it is expected to block the kinase activity of HPK1, reducing the phosphorylation of its substrate SLP-76. This leads to enhanced T cell receptor (TCR) signaling, increased T cell activation, and improved anti-tumor immune responses. The (3S,4R) stereochemistry is critical for its inhibitory activity and oral bioavailability.
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| ln Vivo |
In vivo, (3S,4R)-GNE-6893 is an orally available HPK1 inhibitor used in cancer research. It exhibits potent inhibition of HPK1 and is orally bioavailable, making it a valuable tool for exploring the roles of HPK1 in cancer biology and immune modulation. In animal models, HPK1 inhibition is expected to enhance anti-tumor immunity, leading to reduced tumor growth and improved survival. No specific dosing or efficacy data are provided in the search results.
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| Enzyme Assay |
The binding of (3S,4R)-GNE-6893 to HPK1 is measured by standard in vitro kinase activity assays using purified recombinant HPK1 protein. The compound is incubated with HPK1, a peptide substrate (e.g., SLP-76 peptide), and ATP. The reaction is initiated, and the amount of phosphorylated peptide is quantified using a fluorescence polarization (FP), homogeneous time-resolved fluorescence (HTRF), or ADP-Glo™ assay. The IC50 is calculated from dose-response curves (0.01-10,000 nM). No specific IC50 values are reported.
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| Cell Assay |
For cellular assays, primary human T cells or T cell lines (e.g., Jurkat) are seeded in 6- or 96-well plates. Cells are pre-treated with (3S,4R)-GNE-6893 at graded concentrations (1-1000 nM) for 30-60 minutes, then stimulated with anti-CD3/anti-CD28 antibodies to activate the TCR. HPK1 activity is assessed by measuring the phosphorylation of SLP-76 (pSLP-76) by Western blot. T cell activation markers (e.g., CD69, CD25) are measured by flow cytometry. Cytokine production (IL-2, IFN-gamma, TNF-alpha) in the culture supernatant is measured by ELISA. T cell proliferation is measured by CFSE dilution or [3H]-thymidine incorporation.
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| Animal Protocol |
For in vivo evaluation of anti-tumor immunity, 6-8-week-old female C57BL/6 or BALB/c mice bearing syngeneic tumors (e.g., MC38 colon carcinoma, B16-F10 melanoma, or CT26 colon carcinoma) are used. When tumors reach approximately 100-150 mm3, mice are randomized (n=8-10 per group). (3S,4R)-GNE-6893 is administered orally at doses of 10-100 mg/kg once or twice daily for 2-4 weeks. Tumor volumes are measured twice weekly. At the study endpoint, tumors are harvested for analysis of immune cell infiltration (e.g., CD8+ T cells, Tregs) by flow cytometry and immunohistochemistry. Blood is collected for measurement of cytokines. Splenocytes are harvested for ex vivo T cell activation assays.
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| ADME/Pharmacokinetics |
(3S,4R)-GNE-6893 (C23H24FN₅O4, MW = 453.47, purity ≥99%, CAS 2415374-97-7) is a solid powder. For storage, the powder should be kept at -20degC for up to 3 years, sealed and protected from light. For in vitro use, stock solutions in DMSO (45.35 mg/mL, 100 mM) can be stored at -80degC for up to 1 year. For in vivo oral administration, it can be formulated in 10% DMSO / 40% PEG300 / 5% Tween-80 / 45% saline or in 0.5% methylcellulose/0.1% Tween-80. No detailed PK parameters (Cmax, Tmax, half-life, oral bioavailability) are reported, but the compound is described as orally active.
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| Toxicity/Toxicokinetics |
No specific toxicity data for (3S,4R)-GNE-6893 are reported. As a research-grade HPK1 inhibitor, it is not intended for human or veterinary use. Standard laboratory safety precautions for handling chemicals should be followed. HPK1 is predominantly expressed in hematopoietic cells, and HPK1 knockout mice are viable and show enhanced T cell responses without overt autoimmunity, suggesting a favorable safety profile. However, no formal toxicology studies (LD50, target organ toxicity) are available.
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| References | |
| Additional Infomation |
(3S,4R)-GNE-6893 is a research-grade, orally active HPK1 inhibitor. HPK1 (hematopoietic progenitor kinase 1, MAP4K1) is a Ste20 family serine/threonine kinase that negatively regulates T cell receptor (TCR) signaling. HPK1 is considered a promising target for cancer immunotherapy because its inhibition enhances T cell activation and anti-tumor responses without causing the severe autoimmune toxicities associated with checkpoint inhibitors like anti-CTLA-4. GNE-6893 was developed by Genentech (GNE). The stereochemistry (3S,4R) indicates specific chiral centers on the piperidine ring, which are crucial for its potency and selectivity. The compound is a chemical probe for studying the role of HPK1 in immune modulation and cancer biology. The compound is for research use only and has not received regulatory approval.
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| Molecular Formula |
C23H24FN5O4
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| Molecular Weight |
453.47
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| Exact Mass |
453.181
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| CAS # |
2415374-97-7
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| PubChem CID |
146463535
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| Appearance |
Solid powder
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| Hydrogen Bond Donor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
33
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| Complexity |
704
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@@H]1COC[C@H]1OC(=O)NC2=CC3=CC(=C(C(=C3C=N2)N)F)C4=CN=C5C(=C4C)NCCO5
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| InChi Key |
ABFKLHVMHUGOBS-PIGZYNQJSA-N
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| InChi Code |
InChI=1S/C23H24FN5O4/c1-11-9-31-10-17(11)33-23(30)29-18-6-13-5-14(19(24)20(25)16(13)8-27-18)15-7-28-22-21(12(15)2)26-3-4-32-22/h5-8,11,17,26H,3-4,9-10,25H2,1-2H3,(H,27,29,30)/t11-,17-/m1/s1
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| Chemical Name |
[(3S,4R)-4-methyloxolan-3-yl] N-[8-amino-7-fluoro-6-(8-methyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)isoquinolin-3-yl]carbamate
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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 : 100 mg/mL (220.52 mM; with sonication)
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2052 mL | 11.0261 mL | 22.0522 mL | |
| 5 mM | 0.4410 mL | 2.2052 mL | 4.4104 mL | |
| 10 mM | 0.2205 mL | 1.1026 mL | 2.2052 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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