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#redirectCDK_inhibitor#CDK_inhibitors_on_clinical_trials {{R with possibilities}} |
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{{Short description|Chemical compound}}
{{Use American English|date=February 2021}}
{{Use dmy dates|date=February 2021}}
{{Infobox drug
| image = Trilaciclib.svg
| width =
| alt =
| caption =
<!-- Clinical data -->
| pronounce = {{IPAc-en|ˌ|t|r|aɪ|l|ə|ˈ|s|aɪ|k|l|ɪ|b}}<br />{{respell|TRY|lə|SY|klib}}
| tradename = Cosela
| Drugs.com = {{drugs.com|pro|Cosela}}
| MedlinePlus =
| DailyMedID = Trilaciclib
| pregnancy_
| pregnancy_
| pregnancy_category=
| routes_of_administration = [[Intravenous]]
| class = [[CDK inhibitor|Cyclin-dependent kinase (CDK) inhibitor]]
| ATC_prefix = V03
| ATC_suffix = AF12
| ATC_supplemental =
<!-- Legal status -->
| legal_
| legal_
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment =
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment =
| legal_US = Rx-only
| legal_US_comment = <ref name="Cosela FDA label">{{cite web | title=Cosela- trilaciclib injection, powder, lyophilized, for solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4b06922c-498d-4871-a037-84a44e6a6b6c | access-date=17 June 2021}}</ref><ref name="FDA PR" />
| legal_EU =
| legal_EU_comment =
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = <!-- For countries not listed above -->
<!-- Pharmacokinetic data -->
| bioavailability =
| protein_bound =
| metabolism =
| metabolites =
| onset =
| elimination_half-life =
| duration_of_action =
| excretion =
<!-- Identifiers -->
| CAS_number_Ref =
| CAS_number = 1374743-00-6
| CAS_supplemental =
| PubChem = 68029831
| IUPHAR_ligand =
| DrugBank_Ref =
| DrugBank = DB15442
| ChemSpiderID_Ref =
| ChemSpiderID = 58825997
| UNII_Ref =
| UNII = U6072DO9XG
| KEGG_Ref =
| KEGG = D11130
| ChEBI_Ref =
| ChEBI =
| ChEMBL_Ref =
| ChEMBL = 3894860
| NIAID_ChemDB =
| PDB_ligand =
| synonyms =
<!-- Chemical and physical data -->
| IUPAC_name = 4-[<nowiki/>[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.0<sup>2,7</sup>]trideca-2,4,6,8-tetraene-13,1'-cyclohexane]-10-one
| C = 24 | H = 30 | N = 8 | O = 1
| SMILES = CN1CCN(CC1)C1=CN=C(NC2=NC3=C(C=C4N3C3(CCCCC3)CNC4=O)C=N2)C=C1
| StdInChI = 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)
| StdInChI_comment =
| StdInChIKey = PDGKHKMBHVFCMG-UHFFFAOYSA-N
| density =
| density_notes =
| melting_point =
| melting_high =
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| sol_units =
| specific_rotation =
}}
'''Trilaciclib''', sold under the brand name '''Cosela''', is a [[medication]] used to reduce the frequency of chemotherapy-induced bone marrow suppression.<ref name="Cosela FDA label" /><ref name="FDA PR">{{cite press release | title=FDA Approves Drug to Reduce Bone Marrow Suppression Caused by Chemotherapy | website=U.S. [[Food and Drug Administration]] (FDA) | date=12 February 2021 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-drug-reduce-bone-marrow-suppression-caused-chemotherapy | access-date=12 February 2021}} {{PD-notice}}</ref><ref>{{cite press release | title=FDA Approves G1 Therapeutics' Cosela (trilaciclib): The First and Only Myeloprotection Therapy to Decrease the Incidence of Chemotherapy-Induced Myelosuppression | publisher=G1 Therapeutics | via=GlobeNewswire | date=12 February 2021 | url=https://www.globenewswire.com/news-release/2021/02/13/2175184/0/en/FDA-Approves-G1-Therapeutics-COSELA-trilaciclib-The-First-and-Only-Myeloprotection-Therapy-to-Decrease-the-Incidence-of-Chemotherapy-Induced-Myelosuppression.html | access-date=12 February 2021}}</ref><ref name="Dhillon_2021">{{cite journal | vauthors = Dhillon S | title = Trilaciclib: First Approval | journal = Drugs | volume = 81 | issue = 7 | pages = 867–874 | date = May 2021 | pmid = 33861388 | doi = 10.1007/s40265-021-01508-y | s2cid = 233258487 }}</ref>
The most common side effects include fatigue; low levels of calcium, potassium and phosphate; increased levels of an enzyme called aspartate aminotransferase; headache; and infection in the lungs (pneumonia).<ref name="FDA PR" />
Trilaciclib may help protect bone marrow cells from damage caused by chemotherapy by inhibiting [[cyclin-dependent kinase]] 4/6, a type of enzyme.<ref name="FDA PR" /> Trilaciclib is the first therapy in its class and was approved for medical use in the United States in February 2021.<ref name="FDA PR"/><ref>{{cite web | title=Drug Approval Package: Cosela | website=U.S. [[Food and Drug Administration]] (FDA) | date=12 March 2021 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000TOC.cfm | access-date=13 September 2021}}</ref> The U.S. [[Food and Drug Administration]] considers it to be a [[first-in-class medication]].<ref name="New Drug Therapy Approvals 2021">{{cite report | title=Advancing Health Through Innovation: New Drug Therapy Approvals 2021 | website=U.S. [[Food and Drug Administration]] (FDA) | date=13 May 2022 | url=https://www.fda.gov/media/155227/download | format=PDF | access-date=22 January 2023 | archive-date=6 December 2022 | archive-url=https://web.archive.org/web/20221206210020/https://www.fda.gov/media/155227/download | url-status=live }} {{PD-notice}}</ref>
Chemotherapy drugs are designed to kill cancer cells but can damage normal tissues as well.<ref name="FDA PR" /> The bone marrow is particularly susceptible to chemotherapy damage.<ref name="FDA PR" /> The bone marrow makes red blood cells, white blood cells, and platelets (small fragments in the blood) that transport oxygen, fight infection, and stop bleeding.<ref name="FDA PR" /> When damaged, the bone marrow produces fewer of these cells, leading to fatigue, increased risk of infection, and bleeding, among other problems.<ref name="FDA PR" /> Trilaciclib may help protect the normal bone marrow cells from the harmful effects of chemotherapy.<ref name="FDA PR" />
== Medical uses ==
Trilaciclib is [[Indication (medicine)|indicated]] to reduce the frequency of chemotherapy-induced bone marrow suppression in adults receiving certain types of chemotherapy for extensive-stage (when the cancer has spread beyond the lungs) small cell lung cancer.<ref name="Cosela FDA label" /><ref name="FDA PR" />
== History ==
The effectiveness of trilaciclib was evaluated in three randomized, double-blind, placebo-controlled studies in participants with extensive-stage small cell lung cancer.<ref name="FDA PR" /> Combined, these studies randomly assigned 245 participants to receive either an infusion of trilaciclib in their veins or a placebo before chemotherapy.<ref name="FDA PR" /> The studies then compared the two groups for the proportion of participants with severe neutropenia (a very low count of white blood cells called neutrophils) and the duration of severe neutropenia in the first cycle of chemotherapy.<ref name="FDA PR" /> In all three studies, participants who received trilaciclib had a lower chance of having severe neutropenia compared to participants who received a placebo.<ref name="FDA PR" /> Among those who had severe neutropenia, participants who received trilaciclib, on average, had it for a shorter time than participants who received a placebo.<ref name="FDA PR" />
The U.S. [[Food and Drug Administration]] (FDA) granted the application for trilaciclib [[priority review]] and [[breakthrough therapy]] designations.<ref name="FDA PR" /> The FDA granted the approval of Cosela to G1 Therapeutics, Inc.<ref name="FDA PR" />
== References ==
{{reflist}}
{{HHS content|url=https://www.fda.gov/}}
== External links ==
* {{ClinicalTrialsGov|NCT03041311|Carboplatin, Etoposide, and Atezolizumab With or Without Trilaciclib (G1T28), a CDK 4/6 Inhibitor, in Extensive Stage Small Cell Lung Cancer (SCLC)}}
* {{ClinicalTrialsGov|NCT02499770|Trilaciclib (G1T28), a CDK 4/6 Inhibitor, in Combination With Etoposide and Carboplatin in Extensive Stage Small Cell Lung Cancer (SCLC)}}
* {{ClinicalTrialsGov|NCT02514447|Trilaciclib (G1T28), a CDK 4/6 Inhibitor, in Patients With Previously Treated Extensive Stage SCLC Receiving Topotecan Chemotherapy}}
{{Detoxifying agents for antineoplastic treatment}}
{{Portal bar | Medicine}}
[[Category:Protein kinase inhibitors]]
[[Category:Chemotherapeutic adjuvants]]
[[Category:Pyridines]]
[[Category:Piperazines]]
[[Category:Spiro compounds]]
[[Category:Amides]]
[[Category:Guanidines]]
[[Category:CDK inhibitors]]
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