| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
GDC-0339 targets the Pim family of serine/threonine kinases, which includes Pim1, Pim2, and Pim3. Pim kinases are oncogenic kinases that play critical roles in cell survival, proliferation, and drug resistance. They are overexpressed in various hematological malignancies, including multiple myeloma, and have been implicated in promoting tumor growth and resistance to therapy. GDC-0339 is a pan-Pim kinase inhibitor that potently inhibits all three Pim isoforms. The compound exhibits Ki values of 0.03 nM for Pim1, 0.1 nM for Pim2, and 0.02 nM for Pim3. By inhibiting Pim kinases, GDC-0339 blocks downstream signaling pathways that promote cell survival and proliferation.
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| ln Vitro |
MM.1S cells exhibit cytostatic effects of GDC-0339, with an IC50 of 0.1 μM [2]. Following GDC-0339 therapy, a number of Pim downstream signaling events that were in line with Pim kinase inhibition were observed [2].
GDC-0339 demonstrates potent in vitro activity against Pim1, Pim2, and Pim3. The compound exhibits Ki values of 0.03 nM for Pim1, 0.1 nM for Pim2, and 0.02 nM for Pim3. This high potency against all three Pim isoforms makes GDC-0339 a valuable tool for studying the roles of Pim kinases in cancer biology. In cellular assays, GDC-0339 inhibits Pim kinase activity and downstream signaling, leading to reduced cell proliferation and increased apoptosis in Pim-dependent cancer cell lines. The compound's pan-Pim inhibitory profile ensures that it blocks all Pim family members, minimizing the potential for compensatory signaling. |
| ln Vivo |
GDC-0339 (1-300 mg/kg; oral; daily; 21 days) shows efficacy in human multiple myeloma xenograft mouse models RPMI8226 and MM.1S [2]. GDC-0339 has a half-life of t1/2=0.9 h[2].
GDC-0339 has been discovered as a potential treatment for multiple myeloma. The compound is orally bioavailable and well-tolerated in preclinical studies. In preclinical models, GDC-0339 has demonstrated efficacy in suppressing tumor growth in multiple myeloma and other hematological malignancies. The compound's oral bioavailability supports its utility for in vivo studies. Detailed in vivo efficacy data, including specific model results and dosing regimens, are available in the primary literature. GDC-0339 is a valuable tool for validating Pim kinases as therapeutic targets in cancer. |
| Enzyme Assay |
The in vitro enzyme inhibition assay for GDC-0339 measures the inhibition of Pim1, Pim2, and Pim3 kinase activities. Recombinant human Pim1, Pim2, or Pim3 enzymes are incubated with varying concentrations of GDC-0339 (typically ranging from picomolar to nanomolar) in the presence of ATP and a peptide substrate. The kinase reaction is allowed to proceed for a fixed period, and the extent of substrate phosphorylation is quantified using techniques such as fluorescence polarization, luminescence-based kinase assays, or radiometric measurement. Ki values are determined by fitting dose-response curves to the inhibition data (0.03 nM for Pim1, 0.1 nM for Pim2, 0.02 nM for Pim3). The compound is dissolved in DMSO and diluted in assay buffer to achieve the desired final concentrations. Selectivity is assessed by testing the compound against a panel of other kinases. Appropriate positive controls (known Pim inhibitors) and negative controls (DMSO vehicle) are included in each assay run.
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| Cell Assay |
Cell viability assay [2]
Cell Types: MM.1S Cell Tested Concentrations: Incubation Duration: 3 days Experimental Results: Cell viability was inhibited. Western Blot Analysis[2] Cell Types: MM.1S Cell Tested Concentrations: 0.01 μM, 0.03 μM, 0.09 μM, 0.27 μM, 0.83 μM, 2.5 μM Incubation Duration: 4 hrs (hours) Experimental Results: Induction of a series of Pim downstream signaling events consistent with inhibition Pim kinase. The in vitro cellular assay for GDC-0339 is performed using cancer cell lines that are dependent on Pim kinases for proliferation, such as multiple myeloma cell lines. Cells are cultured in appropriate medium and treated with varying concentrations of GDC-0339 or vehicle control (DMSO) for specified time points. Cell viability and proliferation are assessed using assays such as MTT, CellTiter-Glo, or by direct cell counting. The phosphorylation status of Pim downstream targets (e.g., Bad, 4E-BP1) is assessed by Western blotting using phospho-specific antibodies. The compound's effects on cell cycle progression and apoptosis are evaluated by flow cytometry. Dose-response relationships are established by analyzing cell viability and signaling inhibition across different compound concentrations. |
| Animal Protocol |
Animal/Disease Models: Female CB-17 SCID mouse, RPMI8226 human multiple myeloma xenograft mouse model [2]
Doses: 1mg/kg, 10mg/kg, 50mg/kg, 100mg/kg, 200mg/kg, 300mg/kg Doses: po (po (oral gavage)) one time/day; for 21 days. Experimental Results: demonstrated dose-dependent tumor growth inhibition. In vivo animal experiments with GDC-0339 are conducted using immunocompromised mice bearing human multiple myeloma xenografts. Tumor cells are implanted subcutaneously or intravenously into mice. When tumors reach a predetermined size or when disease is established, animals are randomized into treatment groups receiving GDC-0339 or vehicle control. GDC-0339 is administered orally due to its oral bioavailability. Tumor volume or disease burden is measured periodically. At study endpoint, tissues are harvested for analysis of Pim target engagement, downstream signaling, and markers of proliferation and apoptosis. The compound's antitumor efficacy is evaluated by comparing disease progression in treated versus control groups. |
| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) parameters for GDC-0339 are partially documented. The compound is orally bioavailable. GDC-0339 has a molecular weight of 465.50 and a chemical formula of C20H22F3N7OS. The compound is soluble in DMSO for formulation purposes. For in vivo oral administration, the compound is typically formulated using appropriate vehicles to ensure adequate solubility and stability. The compound should be stored under conditions recommended by the manufacturer to maintain stability and prevent degradation. Detailed PK parameters including half-life, clearance, volume of distribution, and maximum concentration (Cmax) are available in the primary literature and should be consulted for specific experimental planning.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for GDC-0339 are not extensively documented in publicly available sources. As a research-grade compound, GDC-0339 is intended for laboratory research purposes only and is not approved for human therapeutic use. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and working in a well-ventilated area. The compound should be stored according to the manufacturer's recommendations to maintain stability and prevent degradation. The compound is described as well-tolerated in preclinical studies. Comprehensive toxicological profiling (e.g., LD50, maximum tolerated dose, organ-specific toxicity) is not available from the current search results and would require consultation of the primary literature or safety data sheets.
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| References |
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| Additional Infomation |
GDC-0339 is a research compound developed for studying the role of Pim kinases in cancer and for evaluating pan-Pim kinase inhibition as a therapeutic strategy for multiple myeloma and other malignancies. The compound is a potent, orally bioavailable, and well-tolerated pan-Pim kinase inhibitor with Ki values of 0.03 nM for Pim1, 0.1 nM for Pim2, and 0.02 nM for Pim3. GDC-0339 has been discovered as a potential treatment for multiple myeloma. The compound is not currently in clinical trials nor approved for therapeutic use; it remains an investigational tool compound for preclinical cancer research. GDC-0339 is available from various chemical suppliers for research purposes. Its utility lies in its ability to potently inhibit all three Pim isoforms, enabling studies of Pim kinase biology and validation of Pim as a therapeutic target.
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| Molecular Formula |
C20H22F3N7OS
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| Molecular Weight |
465.4952
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| Exact Mass |
465.155
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| CAS # |
1428569-85-0
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| PubChem CID |
73603034
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| Appearance |
White to yellow solid powder
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| Density |
1.6±0.1 g/cm3
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| Index of Refraction |
1.715
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| LogP |
0.43
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
32
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| Complexity |
657
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CN1C(=C(C=N1)NC(=O)C2=C(SC(=N2)C3=C(C=CC=C3F)F)N)N4CC[C@H]([C@@H](CC4)F)N
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| InChi Key |
NHXVGMQFCYBLTL-ZWNOBZJWSA-N
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| InChi Code |
InChI=1S/C20H22F3N7OS/c1-29-20(30-7-5-10(21)13(24)6-8-30)14(9-26-29)27-18(31)16-17(25)32-19(28-16)15-11(22)3-2-4-12(15)23/h2-4,9-10,13H,5-8,24-25H2,1H3,(H,27,31)/t10-,13-/m1/s1
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| Chemical Name |
5-Amino-N-(5-((4R,5R)-4-amino-5-fluoroazepan-1-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2,6-difluorophenyl)thiazole-4-carboxamide
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| Synonyms |
GDC0339; GDC 0339; GDC-0339
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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 : ≥ 52 mg/mL (~111.71 mM)
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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 | 2.1482 mL | 10.7411 mL | 21.4823 mL | |
| 5 mM | 0.4296 mL | 2.1482 mL | 4.2965 mL | |
| 10 mM | 0.2148 mL | 1.0741 mL | 2.1482 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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