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Purity: ≥98%
Lerociclib dihydrochloride (G1T38) is a potent, selective and orally bioactive CDK4/CDK6 inhibitor with IC50s of 1 nM and 2 nM for CDK4/CyclinD1 and CDK6/CyclinD3, respectively. G1T38 is a competitive, nanomolar inhibitor of CDK4/6 with highly selectivity for CDK4-cyclin D1 and CDK6-cyclin D3. G1T38 exhibits a low EC50 (<100 in='' rb='' competent='' cell='' lines='' compared='' to=''>3 μM in Rb null cells. In vivo, daily oral treatment with G1T38 causes significant, durable growth inhibition of tumors in a HER2/neu GEMM and in MCF7 xenograft breast cancer models.
| ln Vitro |
Lerocyclib has a biological IC50 that is almost thirty times greater than that of CDK4/cyclin D1 and CDK9/cyclin T, making it the least selective of the CDK family for CDK9/cyclin T. In CDK4/6-dependent cells, lerociclib causes a strong and long-lasting G1 arrest at an EC50 of about 20 nM. Upon treatment with G1T38 for 24 hours, WM2664 cells that were dependent on CDK4/6 showed a dose-dependent rise in G1 phase cells. A 300-fold increase over the biological IC50 was achieved by maintaining this inhibition up to 300 nM. Lerociclib at concentrations between 30 and 1000 nM completely inhibited RB phosphorylation in WM2664 cells for a full day as compared to the vehicle control. In just one hour, G1T38 therapy decreased RB phosphorylation, and in sixteen hours, it nearly entirely suppressed it. At EC50 values as low as 23 nM, G1T38 exhibits a strong suppressive effect on the growth of several tumor cell lines, such as those from breast cancer, melanoma, leukemia, and lymphoma [1].
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| ln Vivo |
Lerociclib-treated mice in this HER2+ breast cancer model showed 8% tumor shrinkage after 21 days of treatment, but the tumor burden in control animals increased by 577% during the same period of time. In the MCF7 xenograft model, mice treated with 100 mg/kg Lerociclib or palbociclib daily demonstrated tumor regression within 10 days in comparison to mice given with vehicle. Tumor growth inhibition was seen after 27 days of treatment in the groups receiving 10, 50, and 100 mg/kg of lerociclib (about 12%, 74%, and 90% inhibition, respectively). Tumor growth inhibition of 18%, 66%, and 87% was observed in the 10, 50, and 100 mg/kg dosing groups, respectively, following daily oral palbociclib treatment. It's interesting to note that at the 50 mg/kg dose, lerociclib proved to be far more effective than palbociclib. In the ER+ ZR-75-1 breast cancer xenograft model, Lerocyclib and Palbociclib at the 50 mg/kg dose showed comparable outcomes. Lerociclib alone is quite successful in this NSCLC tumor model, as seen by the 77% TGI and 60% total tumor growth delay shown by Lerociclib-treated mice [1].
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| References |
[1]. Bisi JE, et al. Preclinical development of G1T38: A novel, potent and selective inhibitor of cyclin dependent kinases 4/6 for use as an oral antineoplastic in patients with CDK4/6 sensitive tumors. Oncotarget. 2017 Jun 27;8(26):42343-42358
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| Molecular Formula |
C26H36CL2N8O
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|---|---|
| Molecular Weight |
547.523042678833
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| CAS # |
2097938-59-3
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| Related CAS # |
Lerociclib;1628256-23-4
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| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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| SMILES |
O=C1NCC2(N3C1=CC4=CN=C(NC5=NC=C(N6CCN(C(C)C)CC6)C=C5)N=C43)CCCCC2.[H]Cl.[H]Cl
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| InChi Key |
IUIVDLVJNPANBY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H34N8O.2ClH/c1-18(2)32-10-12-33(13-11-32)20-6-7-22(27-16-20)30-25-28-15-19-14-21-24(35)29-17-26(8-4-3-5-9-26)34(21)23(19)31-25/h6-7,14-16,18H,3-5,8-13,17H2,1-2H3,(H,29,35)(H,27,28,30,31)2*1H
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| Chemical Name |
2'-((5-(4-Isopropylpiperazin-1-yl)pyridin-2-yl)amino)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-pyrazino[1',2'
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| Synonyms |
G1T38 dihydrochloride G 1 T 38 dihydrochloride G-1-T-38
dihydrochloride G1T38 2HCl G 1 T 38 2HCl G-1-T-38 2HCl Lerociclib
HCl Lerociclib hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
H2O : ~5 mg/mL (~9.13 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 | 1.8264 mL | 9.1321 mL | 18.2642 mL | |
| 5 mM | 0.3653 mL | 1.8264 mL | 3.6528 mL | |
| 10 mM | 0.1826 mL | 0.9132 mL | 1.8264 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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