Lerociclib
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MedKoo CAT#: 206842

CAS#: 1628256-23-4 (free base)

Description: Lerociclib , also known as G1T38, is an oral, potent and selective CDK4/6 inhibitor for the treatment of Rb competent tumors. Biochemical profiling demonstrates 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 nM) 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.

Chemical Structure

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Lerociclib
CAS# 1628256-23-4 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 206842
Name: Lerociclib
CAS#: 1628256-23-4 (free base)
Chemical Formula: C26H34N8O
Exact Mass: 474.29
Molecular Weight: 474.613
Elemental Analysis: C, 65.80; H, 7.22; N, 23.61; O, 3.37

Price and Availability

Size Price Availability Quantity
5mg USD 90 Ready to ship
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1350 Ready to ship
Bulk inquiry

Related CAS #: 2097938-59-3 (HCl)   1628256-23-4 (free base)  

Synonym: G1T38; G1T-38; G1T 38; G1-T38; G1 T-38; G1 T38; Lerociclib

IUPAC/Chemical Name: 2'-((5-(4-isopropylpiperazin-1-yl)pyridin-2-yl)amino)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-pyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidin]-6'-one

InChi Key: YPJRHEKCFKOVRT-UHFFFAOYSA-N

InChi Code: InChI=1S/C26H34N8O/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)

SMILES Code: CC(C)N(CC1)CCN1C(C=N2)=CC=C2NC3=NC=C4C(N(C5(CCCCC5)CNC6=O)C6=C4)=N3

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: Inhibition of the p16INK4a/cyclin D/CDK4/6/RB pathway is an effective therapeutic strategy for the treatment of estrogen receptor positive (ER+) breast cancer.

Biological target: Lerociclib (G1T38) is a potent and selective inhibitor of CDK4/6, with IC50s of 1 nM, 2 nM for CDK4/CyclinD1 and CDK6/CyclinD3, respectively.
In vitro activity: To examine the therapeutic potential of G1T48, cell proliferation assays were performed using multiple ER-positive breast cancer cell lines (Fig. 3). G1T48 significantly inhibited estrogen-mediated growth of MCF7 cells demonstrating approximately threefold higher potency when compared to fulvestrant (Fig. 3a, Online Resource 5). Additionally, G1T48 and benchmark antiestrogens also inhibited the estrogen-mediated growth of ER-positive BT474 and ZR-75-1 breast cancer cells, while no growth inhibition was observed in ERnegative MDA-MB-436 breast cancer cells (Fig. 3, Online Resource 5). Furthermore, G1T48 does not impact apoptosis in MCF7 breast cancer cells. Thus, G1T48 selectively inhibits the growth of ER-positive, but not ER-negative, breast cancer cells. Reference: Breast Cancer Res Treat. 2020; 180(3): 635–646. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103015/
In vivo activity: The therapeutic potential of G1T48 in ER-positive primary and endocrine refractory breast cancer models was evaluated in vivo. G1T48 was first assessed, as a monotherapy or in combination with the CDK4/6 inhibitor lerociclib, for its impact on the growth of naïve MCF7 xenograft tumors (Fig. 5a). Ovariectomized estrogen-treated female nu/nu mice bearing MCF7 xenograft tumors were randomized to treatment with vehicle, lerociclib (50 mg/kg), and/or G1T48 (30 or 100 mg/kg). G1T48 treatment demonstrated dosedependent repression of tumor growth. Next, ovariectomized tamoxifen-treated mice bearing TamR xenografts were randomized to treatment with lerociclib (50 mg/kg or 100 mg/kg), G1T48 (30 mg/kg or 100 mg/kg), fulvestrant (200 mg/kg), or CDK4/6 inhibitor palbociclib (100 mg/kg) as monotherapies or a combination of lerociclib (50 mg/kg) and G1T48 (30 or 100 mg/kg). G1T48 was found to demonstrate dose-dependent inhibition of TamR tumor growth (Fig. 5c) albeit with less efficacy than fulvestrant. Interestingly, G1T48 treatment resulted in greater downregulation of intratumoral ER levels than fulvestrant despite less efficient inhibition of tumor growth. Reference: Breast Cancer Res Treat. 2020; 180(3): 635–646. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103015

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 1.0 2.11

Preparing Stock Solutions

The following data is based on the product molecular weight 474.61 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Andreano KJ, Wardell SE, Baker JG, Desautels TK, Baldi R, Chao CA, Heetderks KA, Bae Y, Xiong R, Tonetti DA, Gutgesell LM, Zhao J, Sorrentino JA, Thompson DA, Bisi JE, Strum JC, Thatcher GRJ, Norris JD. G1T48, an oral selective estrogen receptor degrader, and the CDK4/6 inhibitor lerociclib inhibit tumor growth in animal models of endocrine-resistant breast cancer. Breast Cancer Res Treat. 2020 Apr;180(3):635-646. doi: 10.1007/s10549-020-05575-9. Epub 2020 Mar 4. PMID: 32130619; PMCID: PMC7103015.
In vitro protocol: 1. Andreano KJ, Wardell SE, Baker JG, Desautels TK, Baldi R, Chao CA, Heetderks KA, Bae Y, Xiong R, Tonetti DA, Gutgesell LM, Zhao J, Sorrentino JA, Thompson DA, Bisi JE, Strum JC, Thatcher GRJ, Norris JD. G1T48, an oral selective estrogen receptor degrader, and the CDK4/6 inhibitor lerociclib inhibit tumor growth in animal models of endocrine-resistant breast cancer. Breast Cancer Res Treat. 2020 Apr;180(3):635-646. doi: 10.1007/s10549-020-05575-9. Epub 2020 Mar 4. PMID: 32130619; PMCID: PMC7103015.
In vivo protocol: 1. Andreano KJ, Wardell SE, Baker JG, Desautels TK, Baldi R, Chao CA, Heetderks KA, Bae Y, Xiong R, Tonetti DA, Gutgesell LM, Zhao J, Sorrentino JA, Thompson DA, Bisi JE, Strum JC, Thatcher GRJ, Norris JD. G1T48, an oral selective estrogen receptor degrader, and the CDK4/6 inhibitor lerociclib inhibit tumor growth in animal models of endocrine-resistant breast cancer. Breast Cancer Res Treat. 2020 Apr;180(3):635-646. doi: 10.1007/s10549-020-05575-9. Epub 2020 Mar 4. PMID: 32130619; PMCID: PMC7103015.

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1: Bisi JE, Sorrentino JA, Jordan JL, Darr DD, Roberts PJ, Tavares FX, Strum JC. 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. doi: 10.18632/oncotarget.16216. PubMed PMID: 28418845; PubMed Central PMCID: PMC5522071.

2: Stice JP, Wardell SE, Norris JD, Yllanes AP, Alley HM, Haney VO, White HS, Safi R, Winter PS, Cocce KJ, Kishton RJ, Lawrence SA, Strum JC, McDonnell DP. CDK4/6 Therapeutic Intervention and Viable Alternative to Taxanes in CRPC. Mol Cancer Res. 2017 Jun;15(6):660-669. doi: 10.1158/1541-7786.MCR-17-0028. Epub 2017 Feb 16. PubMed PMID: 28209757.