Trilaciclib

Identification

Summary

Trilaciclib is a CDK4 and CDK6 inhibitor to reduce the risk of chemotherapy induced myelosuppression.

Brand Names
Cosela
Generic Name
Trilaciclib
DrugBank Accession Number
DB15442
Background

Trilaciclib, or G1T28, is a CDK4 and CDK6 inhibitor, indicated to reduce the incidence of chemotherapy induced myelosuppression in patients before topotecan-containing or platinum and etoposide-containing chemotherapy for extensive stage small cell lung cancer.5 CDK4 and CDK6 inhibitors have been investigated since the mid 1990s for their use in tumorigenesis and chemotherapy.3 Trilaciclib was first described in the literature in 2016.1

Trilaciclib was granted FDA approval on 12 February 2021.4

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 446.559
Monoisotopic: 446.254257618
Chemical Formula
C24H30N8O
Synonyms
  • Trilaciclib
External IDs
  • G1T28

Pharmacology

Indication

Trilaciclib is indicated to reduce the incidence of chemotherapy induced myelosuppression in patients prior to receiving platinum and etoposide-containing or topotecan-containing chemotherapy regimens for extensive-stage small cell lung cancer.5

Pharmacology
Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
Avoid life-threatening adverse drug events
Improve clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events & improve clinical decision support.
Learn more
Pharmacodynamics

Trilaciclib is indicated to reduce the incidence of chemotherapy induced myelosuppression in patients prior to receiving platinum and etoposide-containing or topotecan-containing chemotherapy regimens for extensive-stage small cell lung cancer.5 It has a short duration of action of approximately 16 hours, and a narrow therapeutic index.1,5 Patients should be counselled regarding the risk of injection site reactions, hypersensitivity, and interstitial lung disease.5

Mechanism of action

Trilaciclib is inhibits cyclin-dependant kinase 4 (CDK4) at a concentration of 1 nmol/L and cyclin-dependent kinase 5 (CDK5) at 4 nmol/L.1,5 Inhibition of CDK2, CDK5, and CDK7 is over 1000-fold less at these concentrations and inhibition of CDK9 is 50-fold less.1

CDK4 and CDK5 are expressed in hematopoietic stem cells and progenitor cells.2 They are capable of phosphorylating and inactivating the retinoblastoma protien; a tumor suppressor.1,3 When trilaciclib is given to patients with retinoblastoma protein-null small cell lung cancer, it does not interfere with the intended chemotherapy induced cytotoxicity of cancer cells.1 Inhibition of CDK4 and CDK5 leads to a reversible pause in the cell cycle in the G1 phase for approximately 16 hours.1 The temporary cell cycle arrest prevents chemotherapy induced DNA damage in healthy cells, reducing the activity of caspases 3 and 7, which reduces apoptosis of healthy cells.1

Other studies have shown inhibitors of CDK4 and CDK6 enhance T-cell activation, upregulating major histocompatibility complex (MHC) class I and II, and stabilize programmed death-ligand 1 (PD-L1).2 Together these activities increase T-cell activity, increase antigen presentation, and sensitize cells to immune checkpoint inhibitors.2

TargetActionsOrganism
ACyclin-dependent kinase 4
inhibitor
Humans
ACyclin-dependent kinase 6
inhibitor
Humans
NCyclin-dependent kinase 9
inhibitor
Humans
NCyclin-dependent kinase 2
inhibitor
Humans
NCyclin-dependent kinase 5
inhibitor
Humans
NCyclin-dependent kinase 7
inhibitor
Humans
Absorption

Cmax and AUC of trilaciclib increase proportionally with dose.5

Volume of distribution

The volume of distribution of trilaciclib at steady state is 1130 L.5

Protein binding

Data regarding the protein binding of trilaciclib are not readily available.5

Metabolism

Data regarding the metabolism of trilaciclib are not readily available, however it is expected to be extensively metabolised.5

Route of elimination

79.1% of a radiolabelled dose is recovered in the feces, 7% as the unchanged parent compound.5 14% of a radiolabelled dose is recovered in the urine, 2% as the unchanged parent compound.5

Half-life

The mean terminal half life of trilaciblib is approximately 14 h.5

Clearance

The clearance of trilaciclib is 158 L/h.5

Adverse Effects
Adverseeffects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.
Learn more
Improve decision support & research outcomes with our structured adverse effects data.
Learn more
Toxicity

Data regarding overdoses of trilaciclib are not readily available.5 For grade 3 or worse injection site reactions, acute drug hypersensitivity reactions, and interstitial lung disease; or any other grade 4 toxicities; permanently discontinue trilacilib.5

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbemaciclibThe excretion of Abemaciclib can be decreased when combined with Trilaciclib.
AcenocoumarolThe metabolism of Acenocoumarol can be increased when combined with Trilaciclib.
AcetaminophenThe metabolism of Acetaminophen can be increased when combined with Trilaciclib.
AcyclovirThe metabolism of Acyclovir can be increased when combined with Trilaciclib.
AfatinibAfatinib may decrease the excretion rate of Trilaciclib which could result in a higher serum level.
AgomelatineThe metabolism of Agomelatine can be increased when combined with Trilaciclib.
AlbendazoleThe metabolism of Albendazole can be increased when combined with Trilaciclib.
AlectinibAlectinib may decrease the excretion rate of Trilaciclib which could result in a higher serum level.
AlosetronThe metabolism of Alosetron can be increased when combined with Trilaciclib.
AmantadineThe serum concentration of Amantadine can be increased when it is combined with Trilaciclib.
Interactions
Identify potential medication risks
Easily compare up to 40 drugs with our drug interaction checker.
Get severity rating, description, and management advice.
Learn more
Food Interactions
No interactions found.

Products

Products2
Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Trilaciclib dihydrochloride4BX07W725T1977495-97-8BRCYOXKEDFAUSA-UHFFFAOYSA-N
International/Other Brands
Cosela (G1 Therapeutics, Inc.)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CoselaInjection, powder, lyophilized, for solution300 mg/20mLIntravenousG1 Therapeutics, Inc.2021-02-12Not applicableUS flag

Categories

Drug Categories
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
U6072DO9XG
CAS number
1374743-00-6
InChI Key
PDGKHKMBHVFCMG-UHFFFAOYSA-N
InChI
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)
IUPAC Name
12'-{[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino}-2',5',11',13'-tetraazaspiro[cyclohexane-1,3'-tricyclo[7.4.0.0^{2,7}]tridecane]-1'(9'),7',10',12'-tetraen-6'-one
SMILES
CN1CCN(CC1)C1=CN=C(NC2=NC3=C(C=C4N3C3(CCCCC3)CNC4=O)C=N2)C=C1

References

General References
  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.MCT-15-0775. Epub 2016 Jan 29. [Article]
  2. Lai AY, Sorrentino JA, Dragnev KH, Weiss JM, Owonikoko TK, Rytlewski JA, Hood J, Yang Z, Malik RK, Strum JC, Roberts PJ: CDK4/6 inhibition enhances antitumor efficacy of chemotherapy and immune checkpoint inhibitor combinations in preclinical models and enhances T-cell activation in patients with SCLC receiving chemotherapy. J Immunother Cancer. 2020 Oct;8(2). pii: jitc-2020-000847. doi: 10.1136/jitc-2020-000847. [Article]
  3. Peters G: The D-type cyclins and their role in tumorigenesis. J Cell Sci Suppl. 1994;18:89-96. doi: 10.1242/jcs.1994.supplement_18.13. [Article]
  4. FDA News Release: FDA Approves Drug to Reduce Bone Marrow Suppression Caused by Chemotherapy [Link]
  5. FDA Approved Drug Products: Cosela (Trilaciclib) Intravenous Injection [Link]
ChemSpider
58825997
BindingDB
253928
RxNav
2479690
ChEMBL
CHEMBL3894860
Wikipedia
CDK_inhibitor

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3RecruitingTreatmentBreast Cancer / Breast Cancer (Triple Negative Breast Cancer (TNBC))1
3RecruitingTreatmentChemotherapeutic Toxicity / Metastatic Colorectal Cancer (CRC) / Myelosuppression Adult1
3RecruitingTreatmentExtensive-stage Small Cell Lung Cancer (SCLC)1
2Active Not RecruitingTreatmentBreast Cancer / Breast Cancer (Triple Negative Breast Cancer (TNBC)) / Breast Neoplasms, Triple-Negative / Neoplasms, Breast1
2Active Not RecruitingTreatmentSmall Cell Lung Cancer (SCLC)1
2RecruitingTreatmentBladder Cancer, Cancer / Chemotherapy Induced Neutropenia / Metastatic Bladder Cancer / Myelosuppression Adult / Transitional Cell, Carcinoma1
2RecruitingTreatmentBreast Cancer / Breast Cancer (Triple Negative Breast Cancer (TNBC)) / Early Breast Cancer / Hemangiosarcoma / HER 2 Negative Breast Cancer / HER2/Neu-positive Breast Cancer / Hormone Receptor Negative Tumor / Hormone Receptor Positive Tumor / Locally Advanced Breast Cancer (LABC) / Neoplasms, Breast / Tumors, Breast1
2RecruitingTreatmentLung Cancers / Metastatic Non-Small Cell Lung Cancer / Non-Small Cell Lung Carcinoma (NSCLC)1
1CompletedOtherHealthy Subjects (HS)1
1, 2Active Not RecruitingTreatmentSmall Cell Lung Cancer (SCLC)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous300 mg/20mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US9487530No2014-03-142034-03-14US flag
US10085992No2014-03-142034-03-14US flag
US8598197No2011-10-252031-10-25US flag
US8598186No2011-10-252031-10-25US flag
US10927120No2011-10-252031-10-25US flag
US9957276No2011-10-252031-10-25US flag
US10189849No2011-10-252031-10-25US flag
US10189850No2011-10-252031-10-25US flag
US10966984No2014-03-142034-03-14US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.26 mg/mLALOGPS
logP2.85ALOGPS
logP2.74ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)11.59ChemAxon
pKa (Strongest Basic)7.65ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area91.21 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity128.51 m3·mol-1ChemAxon
Polarizability50.52 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Drugtargets2
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Cyclin-dependent protein serine/threonine kinase regulator activity
Specific Function
Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S tra...
Gene Name
CDK4
Uniprot ID
P11802
Uniprot Name
Cyclin-dependent kinase 4
Molecular Weight
33729.55 Da
References
  1. Weiss JM, Csoszi T, Maglakelidze M, Hoyer RJ, Beck JT, Domine Gomez M, Lowczak A, Aljumaily R, Rocha Lima CM, Boccia RV, Hanna W, Nikolinakos P, Chiu VK, Owonikoko TK, Schuster SR, Hussein MA, Richards DA, Sawrycki P, Bulat I, Hamm JT, Hart LL, Adler S, Antal JM, Lai AY, Sorrentino JA, Yang Z, Malik RK, Morris SR, Roberts PJ, Dragnev KH: Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial. Ann Oncol. 2019 Oct 1;30(10):1613-1621. doi: 10.1093/annonc/mdz278. [Article]
  2. Daniel D, Kuchava V, Bondarenko I, Ivashchuk O, Reddy S, Jaal J, Kudaba I, Hart L, Matitashvili A, Pritchett Y, Morris SR, Sorrentino JA, Antal JM, Goldschmidt J: Trilaciclib prior to chemotherapy and atezolizumab in patients with newly diagnosed extensive-stage small cell lung cancer: A multicentre, randomised, double-blind, placebo-controlled Phase II trial. Int J Cancer. 2020 Dec 21. doi: 10.1002/ijc.33453. [Article]
  3. Lai AY, Sorrentino JA, Dragnev KH, Weiss JM, Owonikoko TK, Rytlewski JA, Hood J, Yang Z, Malik RK, Strum JC, Roberts PJ: CDK4/6 inhibition enhances antitumor efficacy of chemotherapy and immune checkpoint inhibitor combinations in preclinical models and enhances T-cell activation in patients with SCLC receiving chemotherapy. J Immunother Cancer. 2020 Oct;8(2). pii: jitc-2020-000847. doi: 10.1136/jitc-2020-000847. [Article]
  4. Li C, Hart L, Owonikoko TK, Aljumaily R, Rocha Lima CM, Conkling PR, Webb RT, Jotte RM, Schuster S, Edenfield WJ, Smith DA, Sale M, Roberts PJ, Malik RK, Sorrentino JA: Trilaciclib dose selection: an integrated pharmacokinetic and pharmacodynamic analysis of preclinical data and Phase Ib/IIa studies in patients with extensive-stage small cell lung cancer. Cancer Chemother Pharmacol. 2021 Feb 17. pii: 10.1007/s00280-021-04239-9. doi: 10.1007/s00280-021-04239-9. [Article]
  5. Hart LL, Ferrarotto R, Andric ZG, Beck JT, Subramanian J, Radosavljevic DZ, Zaric B, Hanna WT, Aljumaily R, Owonikoko TK, Verhoeven D, Xiao J, Morris SR, Antal JM, Hussein MA: Myelopreservation with Trilaciclib in Patients Receiving Topotecan for Small Cell Lung Cancer: Results from a Randomized, Double-Blind, Placebo-Controlled Phase II Study. Adv Ther. 2021 Jan;38(1):350-365. doi: 10.1007/s12325-020-01538-0. Epub 2020 Oct 29. [Article]
  6. FDA Approved Drug Products: Cosela (Trilaciclib) Intravenous Injection [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Cyclin-dependent protein serine/threonine kinase activity
Specific Function
Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during int...
Gene Name
CDK6
Uniprot ID
Q00534
Uniprot Name
Cyclin-dependent kinase 6
Molecular Weight
36938.025 Da
References
  1. Weiss JM, Csoszi T, Maglakelidze M, Hoyer RJ, Beck JT, Domine Gomez M, Lowczak A, Aljumaily R, Rocha Lima CM, Boccia RV, Hanna W, Nikolinakos P, Chiu VK, Owonikoko TK, Schuster SR, Hussein MA, Richards DA, Sawrycki P, Bulat I, Hamm JT, Hart LL, Adler S, Antal JM, Lai AY, Sorrentino JA, Yang Z, Malik RK, Morris SR, Roberts PJ, Dragnev KH: Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial. Ann Oncol. 2019 Oct 1;30(10):1613-1621. doi: 10.1093/annonc/mdz278. [Article]
  2. Daniel D, Kuchava V, Bondarenko I, Ivashchuk O, Reddy S, Jaal J, Kudaba I, Hart L, Matitashvili A, Pritchett Y, Morris SR, Sorrentino JA, Antal JM, Goldschmidt J: Trilaciclib prior to chemotherapy and atezolizumab in patients with newly diagnosed extensive-stage small cell lung cancer: A multicentre, randomised, double-blind, placebo-controlled Phase II trial. Int J Cancer. 2020 Dec 21. doi: 10.1002/ijc.33453. [Article]
  3. Lai AY, Sorrentino JA, Dragnev KH, Weiss JM, Owonikoko TK, Rytlewski JA, Hood J, Yang Z, Malik RK, Strum JC, Roberts PJ: CDK4/6 inhibition enhances antitumor efficacy of chemotherapy and immune checkpoint inhibitor combinations in preclinical models and enhances T-cell activation in patients with SCLC receiving chemotherapy. J Immunother Cancer. 2020 Oct;8(2). pii: jitc-2020-000847. doi: 10.1136/jitc-2020-000847. [Article]
  4. Li C, Hart L, Owonikoko TK, Aljumaily R, Rocha Lima CM, Conkling PR, Webb RT, Jotte RM, Schuster S, Edenfield WJ, Smith DA, Sale M, Roberts PJ, Malik RK, Sorrentino JA: Trilaciclib dose selection: an integrated pharmacokinetic and pharmacodynamic analysis of preclinical data and Phase Ib/IIa studies in patients with extensive-stage small cell lung cancer. Cancer Chemother Pharmacol. 2021 Feb 17. pii: 10.1007/s00280-021-04239-9. doi: 10.1007/s00280-021-04239-9. [Article]
  5. Hart LL, Ferrarotto R, Andric ZG, Beck JT, Subramanian J, Radosavljevic DZ, Zaric B, Hanna WT, Aljumaily R, Owonikoko TK, Verhoeven D, Xiao J, Morris SR, Antal JM, Hussein MA: Myelopreservation with Trilaciclib in Patients Receiving Topotecan for Small Cell Lung Cancer: Results from a Randomized, Double-Blind, Placebo-Controlled Phase II Study. Adv Ther. 2021 Jan;38(1):350-365. doi: 10.1007/s12325-020-01538-0. Epub 2020 Oct 29. [Article]
  6. FDA Approved Drug Products: Cosela (Trilaciclib) Intravenous Injection [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
Inhibition is 50-fold less than inhibition of CDK4
General Function
Transcription regulatory region dna binding
Specific Function
Protein kinase involved in the regulation of transcription. Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), whic...
Gene Name
CDK9
Uniprot ID
P50750
Uniprot Name
Cyclin-dependent kinase 9
Molecular Weight
42777.155 Da
References
  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.MCT-15-0775. Epub 2016 Jan 29. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
Inhibition is 1000-fold less than inhibition of CDK4
General Function
Metal ion binding
Specific Function
Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, N...
Gene Name
CDK2
Uniprot ID
P24941
Uniprot Name
Cyclin-dependent kinase 2
Molecular Weight
33929.215 Da
References
  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.MCT-15-0775. Epub 2016 Jan 29. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
Inhibition is 1000-fold less than inhibition of CDK4
General Function
Tau-protein kinase activity
Specific Function
Proline-directed serine/threonine-protein kinase essential for neuronal cell cycle arrest and differentiation and may be involved in apoptotic cell death in neuronal diseases by triggering abortive...
Gene Name
CDK5
Uniprot ID
Q00535
Uniprot Name
Cyclin-dependent-like kinase 5
Molecular Weight
33304.125 Da
References
  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.MCT-15-0775. Epub 2016 Jan 29. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
Inhibition is 1000-fold less than inhibition of CDK4
General Function
Transcription coactivator activity
Specific Function
Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. Cyclin-dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the ...
Gene Name
CDK7
Uniprot ID
P50613
Uniprot Name
Cyclin-dependent kinase 7
Molecular Weight
39038.005 Da
References
  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.MCT-15-0775. Epub 2016 Jan 29. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. FDA Approved Drug Products: Cosela (Trilaciclib) Intravenous Injection [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. FDA Approved Drug Products: Cosela (Trilaciclib) Intravenous Injection [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. FDA Approved Drug Products: Cosela (Trilaciclib) Intravenous Injection [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Drug transmembrane transporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
Gene Name
SLC47A2
Uniprot ID
Q86VL8
Uniprot Name
Multidrug and toxin extrusion protein 2
Molecular Weight
65083.915 Da
References
  1. FDA Approved Drug Products: Cosela (Trilaciclib) Intravenous Injection [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. FDA Approved Drug Products: Cosela (Trilaciclib) Intravenous Injection [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. FDA Approved Drug Products: Cosela (Trilaciclib) Intravenous Injection [Link]

Drug created on May 20, 2019 15:32 / Updated on September 15, 2021 23:28