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MedKoo Cat#: 206847 | Name: Trilaciclib
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Trilaciclib is a potential first-in-class short-acting CDK4/6 inhibitor in development to preserve hematopoietic stem cells and enhance immune system function during chemotherapy. Trilaciclib may help protect bone marrow cells from damage caused by chemotherapy by inhibiting cyclin-dependent kinase 4/6, a type of enzyme. Trilaciclib is the first therapy in its class and was approved for medical use in the United States in February 2021.

Chemical Structure

Trilaciclib
Trilaciclib
CAS#1374743-00-6 (free base)

Theoretical Analysis

MedKoo Cat#: 206847

Name: Trilaciclib

CAS#: 1374743-00-6 (free base)

Chemical Formula: C24H30N8O

Exact Mass: 446.2543

Molecular Weight: 446.56

Elemental Analysis: C, 64.55; H, 6.77; N, 25.09; O, 3.58

Price and Availability

Size Price Availability Quantity
5mg USD 150.00 Ready to ship
10mg USD 250.00 Ready to ship
25mg USD 550.00 Ready to ship
50mg USD 950.00 Ready to ship
100mg USD 1,650.00 Ready to ship
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Related CAS #
1374743-00-6 (free base) 1977495-97-8 (HCl)
Synonym
G1T28; G1T-28; G1T 28; Trilaciclib.
IUPAC/Chemical Name
2'-((5-(4-methylpiperazin-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
PDGKHKMBHVFCMG-UHFFFAOYSA-N
InChi Code
InChI=1S/C24H30N8O/c1-30-9-11-31(12-10-30)18-5-6-20(25-15-18)28-23-26-14-17-13-19-22(33)27-16-24(7-3-2-4-8-24)32(19)21(17)29-23/h5-6,13-15H,2-4,7-12,16H2,1H3,(H,27,33)(H,25,26,28,29)
SMILES Code
O=C1NCC2(N3C1=CC4=CN=C(NC5=NC=C(N6CCN(C)CC6)C=C5)N=C43)CCCCC2
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
Conventional cytotoxic chemotherapy is highly effective in certain cancers but causes dose-limiting damage to normal proliferating cells, especially hematopoietic stem and progenitor cells (HSPCs). Serial exposure to cytotoxics causes a long-term hematopoietic compromise ("exhaustion"), which limits the use of chemotherapy and success of cancer therapy.
Biological target:
G1T28 reversibly inhibited CDK4/cyclin D1 and CDK6/cyclin D3 with an IC50 of 1 nmol/L and 4 nmol/L, respectively
In vitro activity:
To demonstrate G1T28-induced G1 arrest decreases chemotherapy-induced damage (i.e., apoptosis or DNA damage), HS68 cells (a surrogate model to represent CDK4/6-dependent HSPCs), were treated with G1T28 and an array of chemotherapies with differing mechanisms of action. Pretreatment of G1T28 in all DNA damaging chemotherapies tested (carboplatin, doxorubicin, etoposide, camptothecin) demonstrated a dose-dependent decrease in γH2AX foci suggesting an attenuation of chemotherapy-induced DNA damage (Fig. 2A). In addition, treatment of HS68 cells with G1T28 prior to chemotherapy treatment (DNA damaging agents previously described, as well as a DNA intercalator; 5-FU and an antimitotic; paclitaxel) elicited a robust dose-dependent decrease in caspase-3/7 activation suggesting an attenuation of apoptosis (Fig. 2B). The data show that a transient G1T28-mediated G1 cell-cycle arrest in CDK4/6-sensitive cells decreases the in vitro toxicity of a variety of commonly used cytotoxic chemotherapy agents associated with myelosuppression. Reference: Mol Cancer Ther. 2016 May;15(5):783-93. https://pubmed.ncbi.nlm.nih.gov/26826116/
In vivo activity:
To directly measure the effect of transient G1 cell-cycle arrest of the HSPCs on chemotherapy-induced bone marrow toxicity, the ability of G1T28 to prevent etoposide-induced apoptosis of bone marrow cells in C57Bl/6 mice was determined. Caspase-3/7 activation increased 3-fold in bone marrow from mice that received etoposide (Fig. 3B), whereas mice that received G1T28 prior to etoposide showed a dose-dependent decrease in caspase-3/7 activation (Fig. 3B). In fact, mice given 100 mg/kg G1T28 30 minutes prior to etoposide treatment, exhibited only background levels of caspase-3/7 activity. These data demonstrate that G1T28 can protect the bone marrow from chemotherapy-induced apoptosis in vivo. Additionally, administration of G1T28 prior to 5-FU produced a faster recovery of all hematopoietic lineages from 5-FU-induced myelosuppression (Fig. 3C). The data demonstrate that treatment with G1T28 prior to 5-FU likely decreases 5-FU-induced damage by chemotherapy in HSPCs, thus accelerating blood count recovery after chemotherapy. Reference: Mol Cancer Ther. 2016 May;15(5):783-93. https://pubmed.ncbi.nlm.nih.gov/26826116/
Solvent mg/mL mM
Solubility
H2O 15.0 33.59
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 446.56 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. Bisi JE, Sorrentino JA, Roberts PJ, Tavares FX, Strum JC. Preclinical Characterization of G1T28: A Novel CDK4/6 Inhibitor for Reduction of Chemotherapy-Induced Myelosuppression. Mol Cancer Ther. 2016 May;15(5):783-93. doi: 10.1158/1535-7163.MCT15-0775. Epub 2016 Jan 29. PMID: 26826116.
In vitro protocol:
1. Bisi JE, Sorrentino JA, Roberts PJ, Tavares FX, Strum JC. Preclinical Characterization of G1T28: A Novel CDK4/6 Inhibitor for Reduction of Chemotherapy-Induced Myelosuppression. Mol Cancer Ther. 2016 May;15(5):783-93. doi: 10.1158/1535-7163.MCT15-0775. Epub 2016 Jan 29. PMID: 26826116.
In vivo protocol:
1. Bisi JE, Sorrentino JA, Roberts PJ, Tavares FX, Strum JC. Preclinical Characterization of G1T28: A Novel CDK4/6 Inhibitor for Reduction of Chemotherapy-Induced Myelosuppression. Mol Cancer Ther. 2016 May;15(5):783-93. doi: 10.1158/1535-7163.MCT15-0775. Epub 2016 Jan 29. PMID: 26826116.
1: Shi W, Wang R, Qian J, Wang L, Li Y, Mi Y, Jia Z, Pan M, Zhang X, Ye W, Xiong F, Hu X, Wang H. Discovery of Potent and Selective CDK4/6 Inhibitors for the Treatment of Chemotherapy-Induced Myelosuppression. J Med Chem. 2025 Jan 6. doi: 10.1021/acs.jmedchem.4c02080. Epub ahead of print. PMID: 39760276. 2: Chen Y, Meng C, Liu L, Liu K, Chen T, Yang C. Myeloprotection effects of trilaciclib in Chinese patients with extensive stage small cell lung cancer (ES- SCLC) receiving chemotherapy-a real-world study. J Thorac Dis. 2024 Nov 30;16(11):7233-7243. doi: 10.21037/jtd-24-893. Epub 2024 Nov 20. PMID: 39678847; PMCID: PMC11635219. 3: Lenz HJ, Liu T, Chen EY, Horváth Z, Bondarenko I, Danielewicz I, Ghidini M, García-Alfonso P, Jones R, Aapro M, Zhang Y, Wang J, Wang W, Adeleye J, Beelen A, Hubbard J. Trilaciclib prior to FOLFOXIRI/bevacizumab for patients with untreated metastatic colorectal cancer: phase 3 PRESERVE 1 trial. JNCI Cancer Spectr. 2025 Jan 3;9(1):pkae116. doi: 10.1093/jncics/pkae116. PMID: 39579142; PMCID: PMC11708780. 4: Shen J, Luo P, Xu J. Adverse event profiles of CDK4/6 inhibitors: data mining and disproportionality analysis of the FDA adverse event reporting system. Ther Adv Drug Saf. 2024 Sep 24;15:20420986241278498. doi: 10.1177/20420986241278498. PMID: 39376495; PMCID: PMC11457275. 5: Muzychka L, Muzychka O, Smolii O. Synthesis and Acetylcholinesterase Inhibitory Activity of Novel Trilaciclib Analogs. Chem Biodivers. 2024 Sep 25:e202401874. doi: 10.1002/cbdv.202401874. Epub ahead of print. PMID: 39320968. 6: Elijah J, Jain P, Holdsworth A, Baron J, Przespolewski E, Wang K, Attwood K, Billias C, Dy GK. Trilaciclib use in extensive-stage small cell lung cancer (ES- SCLC): are clinical benefits seen in the real-world setting? Support Care Cancer. 2024 Aug 31;32(9):622. doi: 10.1007/s00520-024-08828-1. PMID: 39215800; PMCID: PMC11365831. 7: Dubey R, Makhija R, Sharma A, Sahu A, Asati V. Unveiling the promise of pyrimidine-modified CDK inhibitors in cancer treatment. Bioorg Chem. 2024 Aug;149:107508. doi: 10.1016/j.bioorg.2024.107508. Epub 2024 Jun 3. PMID: 38850781. 8: Tan H, Han X, Li C, Liu W, Li K, Sheng X, Qi S. Myelopreservation with Trilaciclib in recurrent advanced ovarian cancer: a case report. Front Oncol. 2024 Apr 22;14:1343239. doi: 10.3389/fonc.2024.1343239. PMID: 38764584; PMCID: PMC11099831. 9: Dai HR, Yang Y, Wang CY, Chen YT, Cui YF, Li PJ, Chen J, Yang C, Jiao Z. Trilaciclib dosage in Chinese patients with extensive-stage small cell lung cancer: a pooled pharmacometrics analysis. Acta Pharmacol Sin. 2024 Oct;45(10):2212-2225. doi: 10.1038/s41401-024-01297-6. Epub 2024 May 17. PMID: 38760542; PMCID: PMC11420218. 10: Hermosilla-Trespaderne M, Hu-Yang MX, Dannoura A, Frey AM, George AL, Trost M, Marín-Rubio JL. Proteomic Analysis Reveals Trilaciclib-Induced Senescence. Mol Cell Proteomics. 2024 Jun;23(6):100778. doi: 10.1016/j.mcpro.2024.100778. Epub 2024 Apr 26. PMID: 38679389; PMCID: PMC11141265. 11: Li C, Preston RA, Dumas E, Beelen A, Marbury TC. Effect of Hepatic Impairment on Trilaciclib Pharmacokinetics. J Clin Pharmacol. 2024 Aug;64(8):975-983. doi: 10.1002/jcph.2435. Epub 2024 Apr 19. PMID: 38639103. 12: Crawford J, Herndon D, Gmitter K, Weiss J. The impact of myelosuppression on quality of life of patients treated with chemotherapy. Future Oncol. 2024;20(21):1515-1530. doi: 10.2217/fon-2023-0513. Epub 2024 Apr 8. PMID: 38587388; PMCID: PMC11441072. 13: Vishakha S, Navneesh N, Kurmi BD, Gupta GD, Verma SK, Jain A, Patel P. An Expedition on Synthetic Methodology of FDA-approved Anticancer Drugs (2018-2021). Anticancer Agents Med Chem. 2024;24(8):590-626. doi: 10.2174/0118715206259585240105051941. PMID: 38288815. 14: Cheng Y, Wu L, Huang D, Wang Q, Fan Y, Zhang X, Fan H, Yao W, Liu B, Yu G, Pan Y, Xu F, He Z, Dong X, Ma R, Min X, Ge X, Chen H, Liu Q, Hu Y, Liu Y, Yang C, Yang Y, Li X, Zhou L. Myeloprotection with trilaciclib in Chinese patients with extensive-stage small cell lung cancer receiving chemotherapy: Results from a randomized, double-blind, placebo-controlled phase III study (TRACES). Lung Cancer. 2024 Feb;188:107455. doi: 10.1016/j.lungcan.2023.107455. Epub 2023 Dec 31. PMID: 38224653. 15: Roskoski R Jr. Properties of FDA-approved small molecule protein kinase inhibitors: A 2024 update. Pharmacol Res. 2024 Feb;200:107059. doi: 10.1016/j.phrs.2024.107059. Epub 2024 Jan 11. PMID: 38216005. 16: Schmitz M, Kaltheuner IH, Anand K, Düster R, Moecking J, Monastyrskyi A, Duckett DR, Roush WR, Geyer M. The reversible inhibitor SR-4835 binds Cdk12/cyclin K in a noncanonical G-loop conformation. J Biol Chem. 2024 Jan;300(1):105501. doi: 10.1016/j.jbc.2023.105501. Epub 2023 Nov 26. PMID: 38016516; PMCID: PMC10767194. 17: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Trilaciclib. 2023 Oct 17. PMID: 37988500. 18: Goldschmidt J, Hart L, Scott J, Boykin K, Bailey R, Heritage T, Lopez- Gonzalez L, Zhou ZY, Edwards ML, Monnette A, Ogbonnaya A, Deyoung K, Venkatasetty D, Shi P, Aton L, Huang H, Conkling PR, Gordan L. Real-World Outcomes of Trilaciclib Among Patients with Extensive-Stage Small Cell Lung Cancer Receiving Chemotherapy. Adv Ther. 2023 Oct;40(10):4189-4215. doi: 10.1007/s12325-023-02601-2. Epub 2023 Jul 25. PMID: 37490258; PMCID: PMC10499684. 19: Zhao S, Zhang H, Yang N, Yang J. A narrative review about CDK4/6 inhibitors in the setting of drug resistance: updates on biomarkers and therapeutic strategies in breast cancer. Transl Cancer Res. 2023 Jun 30;12(6):1617-1634. doi: 10.21037/tcr-22-2807. Epub 2023 Jun 15. PMID: 37434680; PMCID: PMC10331716. 20: Tan AR, O'Shaughnessy J, Cao S, Ahn S, Yi JS. Investigating potential immune mechanisms of trilaciclib administered prior to chemotherapy in patients with metastatic triple-negative breast cancer. Breast Cancer Res Treat. 2023 Sep;201(2):307-316. doi: 10.1007/s10549-023-07009-8. Epub 2023 Jul 7. PMID: 37418031; PMCID: PMC10361859.