Chemical inhibitors of GMD can exert their influence by interfering with the cellular kinases that are pivotal for the cell cycle, where GMD activity is a factor. Alsterpaullone, Roscovitine, Olomoucine, Purvalanol A, and Flavopiridol are all inhibitors targeting various cyclin-dependent kinases (CDKs), which are integral to the regulation of the cell cycle. Alsterpaullone, by inhibiting CDKs, can impede the progression of the cell cycle, leading to an indirect inhibition of GMD, which operates in conjunction with cell cycle phases. Similarly, Roscovitine and Olomoucine target specific CDKs, including CDK1, CDK2, and CDK5. Their inhibitory action can suppress the cell cycle machinery and subsequently GMD's function within that pathway. Purvalanol A extends this inhibition to CDK4, further broadening the scope of cell cycle interruption and, consequently, GMD activity reduction. Flavopiridol, with its wider range against several CDKs, can lead to an extensive blockade of the cell cycle, which would also envelop GMD's associated processes.The rest of the chemicals, including Indirubin-3'-monoxime, 5-Iodotubercidin, PD0332991 (Palbociclib), Dinaciclib, Milciclib, Ribociclib, and Abemaciclib, similarly disrupt GMD activity through their actions on different kinases and related mechanisms. Indirubin-3'-monoxime, as a CDK and GSK-3β inhibitor, not only affects cell cycle progression but also other kinase-related functions, thereby exerting an indirect effect on GMD. 5-Iodotubercidin disrupts the balance of nucleotides by inhibiting adenosine kinase, which could impact GMD's role in DNA synthesis. PD0332991 and Ribociclib, both selective CDK4/6 inhibitors, can arrest the cell cycle in the G1 phase, which is a checkpoint where GMD's downstream activities are regulated. This leads to an indirect inhibition of GMD due to a lack of progression into subsequent cell cycle phases where GMD activity might be necessary. Dinaciclibs broad-spectrum approach against CDKs, including CDK1, CDK2, CDK5, and CDK9, can interrupt both cell cycle and transcriptional regulation, implicating an indirect inhibition of GMD. Milciclib, targeting multiple kinases involved in cell proliferation, can disrupt pathways prerequisite for GMD activity. Lastly, Abemaciclib, like its CDK4/6 inhibitor counterparts, leads to G1-S phase transition arrest, indirectly affecting GMD by holding back the cell cycle conditions that would normally activate GMD.
