Drug Information

Drug (ID: DG01291) and It's Reported Resistant Information

• Name: Trilaciclib
• Synonyms: Trilaciclib; 1374743-00-6; G1T28; UNII-U6072DO9XG; U6072DO9XG; 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; Cosela; 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; Trilaciclib [USAN]; G1T28(Trilaciclib); G1T28 di-HCl; Trilaciclib (USAN/INN); GTPL9626; CHEMBL3894860; SCHEMBL10082028; BDBM253928; BCP25013; EX-A4297; NSC816987; DB15442; NSC-816987; SB19783; US9464092, T; HY-101467; CS-0021431; A17084; D11130; 2'-((5-(4-Methyl-1-piperazinyl)-2-pyridinyl)amino)-7',8'-dihydro-6'H-spiro(cyclohexane-1,9'-pyrazino(1',2':1,5)pyrrolo(2,3-d)pyrimidin)-6'-one; 2-[[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino]spiro[7,8-dihydropyrazino[5,6]pyrrolo[1,2-d]pyrimidine-9,1'-cyclohexane]-6-one; 4-[[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1'-cyclohexane]-10-one; Spiro(cyclohexane-1,9'(6'H)-pyrazino(1',2':1,5)pyrrolo(2,3-d)pyrimidin)-6'-one, 7',8'-dihydro-2'-((5-(4-methyl-1-piperazinyl)-2-pyridinyl)amino)-
• Indication:
  In total 2 Indication(s)
  Small-cell lung cancer [ICD-11: 2C25]; Approved; [1]
  Triple negative breast cancer [ICD-11: 2C60-2C6Y]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Breast cancer [ICD-11: 2C60]; [1]
• Target: Cyclin-dependent kinase 4 (CDK4); CDK4_HUMAN; [1]
• Target: Cyclin-dependent kinase 6 (CDK6); CDK6_HUMAN; [1]
• Formula: C24H30N8O
• IsoSMILES: CN1CCN(CC1)C2=CN=C(C=C2)NC3=NC=C4C=C5C(=O)NCC6(N5C4=N3)CCCCC6
• 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)
• InChIKey: PDGKHKMBHVFCMG-UHFFFAOYSA-N
• PubChem CID: 68029831
• TTD Drug ID: D0AP9E

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Breast cancer [ICD-11: 2C60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Cyclin-dependent kinase 4 (CDK4) [1]

• Molecule Alteration: Function; Inhibition
• Resistant Disease: Triple negative breast cancer [ICD-11: 2C60.9]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: AKT signaling pathway; Activation; hsa04151
• Mechanism Description: Trilaciclib, a small molecule short-acting inhibitor of CDK4/6, has also been approved recently for people with small cell lung cancer, and is also expected to be clinically effective against breast cancer. r\Reducing Rb phosphorylation promotes AKT pathway activity, which may result in CDK4/6 inhibitor resistance. Trilaciclib, an intravenous and competitive CDK4/6 inhibitor, has been shown to reduce the myelotoxicity of chemotherapeutic agents by inducing transient cell cycle arrest. This drug can differentially inhibit both cytotoxic and regulatory T cells.

Key Molecule: Cyclin-dependent kinase 6 (CDK6) [1]

• Molecule Alteration: Function; Inhibition
• Resistant Disease: Triple negative breast cancer [ICD-11: 2C60.9]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: AKT signaling pathway; Activation; hsa04151
• Mechanism Description: Trilaciclib, a small molecule short-acting inhibitor of CDK4/6, has also been approved recently for people with small cell lung cancer, and is also expected to be clinically effective against breast cancer. r\Reducing Rb phosphorylation promotes AKT pathway activity, which may result in CDK4/6 inhibitor resistance. Trilaciclib, an intravenous and competitive CDK4/6 inhibitor, has been shown to reduce the myelotoxicity of chemotherapeutic agents by inducing transient cell cycle arrest. This drug can differentially inhibit both cytotoxic and regulatory T cells.

References

• Ref 1: Potential Prospect of CDK4/6 Inhibitors in Triple-Negative Breast Cancer .Cancer Manag Res. 2021 Jul 1;13:5223-5237. doi: 10.2147/CMAR.S310649. eCollection 2021. 10.2147/CMAR.S310649