| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
HPK1 <0.51 nM (IC50)
|
|---|---|
| ln Vitro |
HPK1-IN-55 (0.5-10000 nM, 5 h) exhibits HPK1 enzyme inhibition in human PBMCs with an IC50 of <0.51 nM and inhibits cellular IL-2 secretion with an EC50 of 43.3 nM[1]. HPK1-IN-55 (0.001-100 nM) stimulates the release of IL-2 and IFN-γ in human PBMCs with EC50 values of 38.8 and 49.2 nM, respectively[1]. HPK1-IN-55 (0.00457-10 μM, 72 h) can promote T cell proliferation at low, medium and high concentrations in human immune T cells[1].
|
| ln Vivo |
HPK1-IN-55 (1.5-12 mg/kg, po, bid, 5 weeks) has good antitumor effects as a monotherapy and shows additive effects in the CT26 model and synergistic effects in the MC38 model when used in combination with anti-PD-1[1]. HPK1-IN-55 (1 mg/kg, iv, 2 mg/kg, po) showed moderate clearance (Clp = 11.41 mL/min/kg), good oral exposure (DNAUC (0−24 h) =560.5 h•ng/mL) and bioavailability (F % = 42.0) in monkeys[1]. HPK1-IN-55 (1.5-12 mg/kg, po, bid, 5 weeks) showed good target engagement in the CT26 model[1]. In vivo pharmacokinetic parameters of HPK1-In-55 HPK1-IN-55 beagle dogs IV Clp (mL/min/kg) Vd (L/kg) 11.44 5.58 beagle dogs PO DNAUC (0-24 h) (h・ng/ml) t1/2 (h) F (%) 563 7.65 41.5 cyno monkeys IV Clp (mL/min/kg) Vd (L/kg) 11.41 5.07 cyno monkeys PO DNAUC (0-24 h) (h・ng/ml) t1/2 (h) F (%) 560.5 8.73 42
|
| Cell Assay |
Cell Proliferation Assay [1]
Cell Types: human pan T cells Tested Tested Concentrations: 0.00457, 0.01372, 0.04115, 0.12346, 0.37037, 1.11111, 3.33333, 10 μM Incubation Duration: 72 h Experimental Results: Increased T cell proliferation at low, intermediate and high Tested Tested Concentrationss in human pan T cells. |
| Animal Protocol |
Animal/Disease Models: Balb/c mice bearing the CT26 murine colorectal cancer tumor[1] .
Doses: 3, 10, or 30 mg/kg Route of Administration: p.o., b.i.d, 24 h Experimental Results: Animals receiving a 10 and 30 mg/kg dose exhibited a free plasma concentration that inhibited pSLP76 > 50% in the spleen for more than 6 h, whereas animals receiving the 3 mg/kg dose did not exhibit this sustained reduction. Animal/Disease Models: Balb/c mice injected with CT26 cells[1] . Doses: 1.5, 12 mg/kg Route of Administration: p.o., b.i.d, 5weeks Experimental Results: Exhibited a good antitumor response with a tumor growth inhibition (TGI) value of 64.3%. Animal/Disease Models: Balb/c mice injected with MC38 cells[1] . Doses: 3, 12 mg/kg Route of Administration: p.o., b.i.d, 5weeks Experimental Results: Demonstrated similar antitumor efficacy in the MC38 model with a TGI value of 34.9% for the 3 mg/kg group and 59.4% for the 12 mg/kg group. |
| References |
| Molecular Formula |
C30H34N8O3
|
|---|---|
| Molecular Weight |
554.64
|
| Exact Mass |
554.275
|
| CAS # |
3048537-58-9
|
| PubChem CID |
172677409
|
| Appearance |
Typically exists as solids at room temperature
|
| Hydrogen Bond Donor Count |
2
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
41
|
| Complexity |
945
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CN1CC2=C(C13CCN(CC3)C4COC4)C=CC(=N2)NC5=CC(=C(N=C5C(=O)N)C6=C7C(=CC=C6)N(C=N7)C)OC
|
| InChi Key |
IKGOYMIPWBVCQZ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C30H34N8O3/c1-36-17-32-26-19(5-4-6-23(26)36)27-24(40-3)13-21(28(35-27)29(31)39)33-25-8-7-20-22(34-25)14-37(2)30(20)9-11-38(12-10-30)18-15-41-16-18/h4-8,13,17-18H,9-12,14-16H2,1-3H3,(H2,31,39)(H,33,34)
|
| Chemical Name |
5-methoxy-6-(1-methylbenzimidazol-4-yl)-3-[[6-methyl-1'-(oxetan-3-yl)spiro[7H-pyrrolo[3,4-b]pyridine-5,4'-piperidine]-2-yl]amino]pyridine-2-carboxamide
|
| 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)
|
| 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
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 | 1.8030 mL | 9.0149 mL | 18.0297 mL | |
| 5 mM | 0.3606 mL | 1.8030 mL | 3.6059 mL | |
| 10 mM | 0.1803 mL | 0.9015 mL | 1.8030 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
