| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
CDK7 ≤50 nM (Ki) CDK2 ≥1000 nM (Ki)
IV-361 targets cyclin-dependent kinase 7 (CDK7), a member of the CDK family that functions as a CDK-activating kinase (CAK). CDK7 phosphorylates and activates other CDKs (CDK1, 2, 4, 6) involved in cell cycle progression and also phosphorylates RNA polymerase II to regulate transcription. Inhibition of CDK7 blocks cell cycle progression and transcription of oncogenes. |
|---|---|
| ln Vitro |
On CDK2 (Ki≥1000 nM) or PLK1 (Ki≥5000 nM), IV-361 exhibits reduced inhibition[1]. Excellent IL-2 and IL-17 production inhibitory activity (all IC50≤100 nM) is demonstrated by IV-361 in peripheral blood mononuclear cells (PBMC)[1]. Excellent HCT-116 cell growth inhibitory action is demonstrated by IV-361 (GI50≤100 nM)[1].
In vitro, IV-361 (0.1-10 uM) inhibits CDK7 activity with Ki ≤50 nM, leading to reduced phosphorylation of CDK substrates (e.g., p-CDK2, p-CDK4, p-RNA pol II). It induces cell cycle arrest at G1/S or G2/M phase and apoptosis in cancer cell lines. The compound may also have anti-inflammatory effects by suppressing cytokine production. |
| ln Vivo |
Orally administered IV-361 (25 mg/kg/day) suppresses tumor volume in female BALB nude mice with HCT-116 at a rate of at least 46%[1].
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| Enzyme Assay |
For non-cellular CDK7 inhibition, purified recombinant human CDK7/cyclin H/MAT1 complex (CAK complex) is incubated with a CDK substrate peptide (e.g., biotinylated CTD peptide from RNA polymerase II) or histone H1, in kinase reaction buffer containing [gamma-32P]ATP. Varying concentrations of IV-361 (0.1-100 uM) are added. Reactions are quenched after 30 minutes, and phosphorylated substrate is captured on filter papers for scintillation counting or by using a homogeneous time-resolved FRET (HTRF) assay.
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| Cell Assay |
For cell-based assays, cancer cell lines (e.g., HCT116, MCF-7, or patient-derived leukemia cells) are seeded in 96-well plates and treated with IV-361 (0.01-10 uM) for 48-72 hours. Cell viability is measured by CellTiter-Glo or MTT. Cell cycle distribution is analyzed by flow cytometry (propidium iodide staining). CDK7 target engagement is assessed by Western blotting for p-CDK2 (Thr160), p-RNA pol II (Ser2 and Ser5), and cleaved caspase-3.
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| Animal Protocol |
For in vivo evaluation, female athymic nude mice are subcutaneously implanted with cancer cells (e.g., HCT116 or MCF-7). When tumors reach 100-200 mm3, IV-361 is administered orally at 10-100 mg/kg once daily for 14-28 days. Tumor volume is measured twice weekly. For autoimmune models, mice with collagen-induced arthritis (CIA) or experimental autoimmune encephalomyelitis (EAE) are dosed orally with IV-361 (10-50 mg/kg) daily. Arthritis scores, paw swelling, and histopathology are assessed.
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| ADME/Pharmacokinetics |
IV-361 is orally active with favorable pharmacokinetic properties supporting once-daily dosing. Detailed PK parameters (Cmax, Tmax, AUC, t½) are described in patent literature (US20190256531A1) but not publicly summarized. The compound has moderate clearance and a half-life compatible with oral administration.
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| Toxicity/Toxicokinetics |
Toxicity data for IV-361 are limited. As a CDK7 inhibitor, potential on-target toxicities may include myelosuppression, gastrointestinal disturbances, and immunosuppression due to inhibition of cell cycle and transcription in normal proliferating tissues. In preclinical studies, IV-361 appears to be well tolerated at effective doses.
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| References |
[1]. Noriaki Iwase, et al. Substituted dihydropyrrolopyrazole derivative. US20190256531A1.
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| Additional Infomation |
IV-361 is a research-grade compound, not approved for human therapy. It is protected by patent US20190256531A1. The compound is being explored for cancer therapy and also for autoimmune and inflammatory diseases based on CDK7's role in cytokine gene transcription (e.g., rheumatoid arthritis, lupus, psoriasis). No clinical trials are registered for IV-361.
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| Molecular Formula |
C23H32FN5O2SI
|
|---|---|
| Molecular Weight |
457.62
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| Exact Mass |
457.23
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| CAS # |
2055741-39-2
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| PubChem CID |
140882977
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
|
| Heavy Atom Count |
32
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| Complexity |
753
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C=C(C=C1)F)NC(=O)N2CC3=C(C2(C)C)NN=C3NC(=O)C4(CCC4)[Si](C)(C)C
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| InChi Key |
FYIUNJAFLWNBAI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H32FN5O2Si/c1-14-8-9-15(24)12-17(14)25-21(31)29-13-16-18(22(29,2)3)27-28-19(16)26-20(30)23(10-7-11-23)32(4,5)6/h8-9,12H,7,10-11,13H2,1-6H3,(H,25,31)(H2,26,27,28,30)
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| Chemical Name |
N-(5-fluoro-2-methylphenyl)-6,6-dimethyl-3-[(1-trimethylsilylcyclobutanecarbonyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide
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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 : 90 mg/mL (196.67 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.25 mg/mL (4.92 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 22.5 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: ≥ 2.25 mg/mL (4.92 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 22.5 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 | 2.1852 mL | 10.9261 mL | 21.8522 mL | |
| 5 mM | 0.4370 mL | 2.1852 mL | 4.3704 mL | |
| 10 mM | 0.2185 mL | 1.0926 mL | 2.1852 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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