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Cell Cycle

In 1953, Howard and Pek had first proposed the cell cycle concept, which constitute an important part of the cell theory. Cells, from the end of the first division to the end of next division, need to go through the same stages of change (namely, G1 → S → G2 → M) again and again. This kind of growth, division of cell is known as the cell cycle. A cell cycle includes mitosis (M) and Interphase (G1, S, and G2). Although the time of each phase of cells is different, but in relative terms, M is the shortest while S phase is much longer.
cell cycle
Figure 1 is a cell cycle

Cell Cycle is series of events in order that ultimately leads to cell growth and division. The cell cycle of eukaryotic can be divided into interphase and cell division phase. During the interphase, the cell accumulates the nutrient and replicated DNA required by mitosis, called mitosis (M) phase. Through studying the molecular mechanism of cell division, the cell division phase can be divided into three phases, G1, S and G2. Therefore, cell cycle consists of four phases: G1, S, G2, and M.

Cells enter G1 phase after being released from mitosis, RNA and protein undergo synthesis during this period, but there is no DNA replication at this stage. The initiation of DNA replication marks the transformation of G1 to S phase. S phase extends to the time when all of the DNA replication has been completed. In the S phase, the composition of all DNA has all changed from diploid 2n to 4n. The end of S phase until mitosis is called G2 phase. During this stage, the cells have two complete sets of diploid chromosomes. The increase of the volume of the nucleus mainly happens in the S phase, when the protein can accumulate and correspond to the replication of DNA. Chromatin is maintained condensed with no visible changes in morphology.

The regulatory proteins of cell cycle are capable of binding to the coding proteins in the cell differentiation period and activate the corresponding protein kinases, thereby promoting cell division. There have been at least found of 11 different types of cyclin, respectively, being A, B1, B2, C, D1, D2, D3, E, F, G and H. Eight of the major cyclin had been separated. Depending on the difference of regulation of the phase of cell cycle through cyclin, it can be divided into G1 phase and M phase two categories. Various types of cyclins all contain a conserved sequence containing about 100 amino acids, called cyclin box, mediating the binding between cyclin and CDK. The animal cell cycles can be regulated by many kinds of cdk- cell cycle protein complexes with the activated CDK1 being able to phosphorylate the target proteins to produce the corresponding physiological effects, such as causing the phosphorylation and further disintegration of lamin, the disappearance of nuclear membrane as well as phosphorylation which leads to the condensation of chromatin.

The result of these effects is the constantly proceeding of the cell cycle. The activation time of various forms of Cdc2 and cdk illustrates a model: the regulatory function of cdk2-G1 cyclin dimer occurs at G1 and S phase while the Cdcc2- cyclin A, B regulating the mitosis (Orlando DA, 2008).

It has been found of many in vivo factors that can stimulate or inhibit cell proliferation, such as a variety of hormones, serum factor, polyamines, proteolytic enzyme, neuraminidase, cAMP, cGMP and diacylglycerol (DG), inositol triphosphate (IP3) and Ca messenger systems. The increased intracellular cAMP concentration has inhibitory effect on the cell proliferation. Those factors that can increase the intracellular cAMP level can all inhibit the proliferation of the cells, decreasing the cell growth; on the contrary, those factors that decrease the intracellular cAMP content can promote DNA synthesis and cell proliferation. The cAMP content of each period of the cell cycle is also not the same (see table).

In the cell line of the Chinese hamster ovary, the content of cAMP in M phase is the minimum, while after M phase, the level of cAMP can increase by three times. From early G1 phase to late G1 phase, the cAMP levels drop down to a moderate level and maintain at a low level until S phase. There are many experiments indicating that cGMP also play regulatory role on cell proliferation. For example, addition of cGMP or dibutyryl cGMP to the 3T3 phase of the G1 phase can induce increased DNA content and promote cell division. For example, raising the level of intracellular cGMP can promote cell mitosis. On the contrary, drugs of mitotic-promoting can also increase the concentration of cGMP. The cAMP can inhibit cell division, promote cell differentiation, cGMP is able to inhibit cell differentiation, promote cell proliferation. In cells of normal growth, cAMP and cGMP can be maintained at an appropriate level, regulating and controlling the operation of the cell cycle (Browne G, 2010).

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Structure Chemical Name CAS MF
Roscovitine Roscovitine 186692-46-6 C19H26N6O
Tozasertib Tozasertib 639089-54-6 C23H28N8OS
SNS-032 SNS-032 345627-80-7 C17H24N4O2S2
AZD 5438 AZD 5438 602306-29-6 C18H21N5O2S
MLN-8237 MLN-8237 1028486-01-2 C27H20ClFN4O4
3-[(Aminocarbonyl)amino]-5-(3-fluorophenyl)-N-(3S)-3-piperidinyl-2-Thiophenecarboxamide 3-[(Aminocarbonyl)amino]-5-(3-fluorophenyl)-N-(3S)-3-piperidinyl-2-Thiophenecarboxamide 860352-01-8 C17H19FN4O2S
Danusertib Danusertib 827318-97-8 C26H30N6O3
Thiazovivin Thiazovivin 1226056-71-8 C15H13N5OS
1H-Pyrazole-3-acetamide, 5-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]-4-quinazolinyl]amino]-N-(3-fluorophenyl)- 1H-Pyrazole-3-acetamide, 5-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]-4-quinazolinyl]amino]-N-(3-fluorophenyl)- 722544-51-6 C26H30FN7O3
BI 2536 BI 2536 755038-02-9 C28H39N7O3
FLAVOPIRIDOL HYDROCHLORIDE FLAVOPIRIDOL HYDROCHLORIDE 131740-09-5 C21H21Cl2NO5
[4-Amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl](2,3-difluoro-6-methoxyphenyl)methanone(R 547) [4-Amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl](2,3-difluoro-6-methoxyphenyl)methanone(R 547) 741713-40-6 C18H21F2N5O4S
GSK1070916 GSK1070916 942918-07-2 C30H33N7O
PHA-680632 PHA-680632 398493-79-3 C28H35N7O2
N-(6-Fluoro-1H-indazol-5-yl)-2-methyl-6-oxo-4-[4-(trifluoromethyl)phenyl]-1,4,5,6-tetrahydro-3-pyridinecarboxamide N-(6-Fluoro-1H-indazol-5-yl)-2-methyl-6-oxo-4-[4-(trifluoromethyl)phenyl]-1,4,5,6-tetrahydro-3-pyridinecarboxamide 864082-47-3 C21H16F4N4O2
Volasertib (BI 6727) Volasertib (BI 6727) 755038-65-4 C34H50N8O3
Y27632 (hydrochloride) Y27632 (hydrochloride) 129830-38-2 C14H23Cl2N3O
2-(4-broMo-2-chlorophenoxy)-N-(4-(N-(4,6-diMethylpyriMidin-2-yl)sulfaMoyl)phenylcarbaMothioyl)acetaMide 2-(4-broMo-2-chlorophenoxy)-N-(4-(N-(4,6-diMethylpyriMidin-2-yl)sulfaMoyl)phenylcarbaMothioyl)acetaMide 587841-73-4 C21H19BrClN5O4S2
PHA 767491 HYDROCHLORIDE PHA 767491 HYDROCHLORIDE 845714-00-3 C12H11N3O
ETHYL 8-METHOXY-2-OXO-2,3,4,5-TETRAHYDRO-1H-BENZO[B]AZEPINE-4-CARBOXYLATE ETHYL 8-METHOXY-2-OXO-2,3,4,5-TETRAHYDRO-1H-BENZO[B]AZEPINE-4-CARBOXYLATE 869363-13-3 C25H15ClF2N4O2
CYC-116 CYC-116 693228-63-6 C18H20N6OS
PF 477736 PF 477736 952021-60-2 C22H25N7O2
CCT129202 CCT129202 942947-93-5 C23H25ClN8OS
PF-03814735 PF-03814735 942487-16-3 C23H25F3N6O2
Abemaciclib mesylate (LY2835219) Abemaciclib mesylate (LY2835219) 1231930-82-7 C28H36F2N8O3S
PD0332991 Isethionate PD0332991 Isethionate 827022-33-3 C26H35N7O6S
Hesperadin Hesperadin 422513-13-1 C29H32N4O3S
SD208 (TGF-Β/SMAD inhibitor) SD208 (TGF-Β/SMAD inhibitor)
HMN-214 HMN-214 173529-46-9 C22H20N2O5S
CHIR-124 CHIR-124 405168-58-3 C23H22ClN5O
BMS-265246 BMS-265246 582315-72-8 C18H17F2N3O2
Ribociclib Ribociclib 1211441-98-3 C23H30N8O
RKI1447 RKI1447 1342278-01-6 C16H14N4O2S
(Z,E)-5-(4-ETHYLBENZYLIDINE)-2-THIOXOTHIAZOLIDIN-4-ONE (Z,E)-5-(4-ETHYLBENZYLIDINE)-2-THIOXOTHIAZOLIDIN-4-ONE 403811-55-2 C12H11NOS2
PHA-793887 PHA-793887 718630-59-2 C19H31N5O2
PURVALANOL A PURVALANOL A 212844-53-6 C19H25ClN6O
TG003 TG003 300801-52-9 C13H15NO2S
GSK461364 GSK461364 929095-18-1 C27H28F3N5O2S
JNJ-7706621 JNJ-7706621 443797-96-4 C15H12F2N6O3S
Aurora A Inhibitor I Aurora A Inhibitor I 1158838-45-9 C31H31ClFN7O2
MK-5108 (VX-689) MK-5108 (VX-689) 1010085-13-8 C22H21ClFN3O3S
CCT 137690 CCT 137690 1095382-05-0 C26H31BrN8O
SCH900776 SCH900776 891494-63-6 C15H18BrN7
MLN0905 MLN0905 1228960-69-7 C24H25F3N6S
4-[(2,6-dichlorobenzoyl)amino]-N-4-piperidinyl1H-pyrazole-3-carboxamide 4-[(2,6-dichlorobenzoyl)amino]-N-4-piperidinyl1H-pyrazole-3-carboxamide 844442-38-2 C16H17Cl2N5O2
AMG 900 AMG 900 945595-80-2 C28H21N7OS
N4-(9-Ethyl-9H-carbazol-3-yl)-N2-(3-Morpholin-4-yl-propyl)-pyriMidine-2,4-diaMine N4-(9-Ethyl-9H-carbazol-3-yl)-N2-(3-Morpholin-4-yl-propyl)-pyriMidine-2,4-diaMine 1380432-32-5 C25H30N6O
ZM 447439 ZM 447439 331771-20-1 C29H31N5O4
PHA-848125 PHA-848125 802539-81-7 C25H32N8O
Ro 3306 Ro 3306 872573-93-8 C18H13N3OS2
LY2603618 LY2603618 911222-45-2 C18H22BrN5O3
XL413 (BMS-863233) XL413 (BMS-863233) 1169562-71-3 C14H13Cl2N3O2
RO3280 RO3280 1062243-51-9 C27H35F2N7O3
Salirasib Salirasib 162520-00-5 C22H30O2S
EHT1864 EHT1864 754240-09-0 C25H27F3N2O4S2HCl
NMS-P937 (NMS1286937) NMS-P937 (NMS1286937) 1034616-18-6 C24H27F3N8O3
LDC000067 LDC000067 1073485-20-7 C18H18N4O3S
SU 9516 SU 9516 377090-84-1 C13H11N3O2
BS-181 HCl BS-181 HCl 1397219-81-6 C22H33ClN6
1-(4-(2-((4-chloro-2-hydroxy-5-iodophenyl)aMino)acetyl)piperazin-1-yl)prop-2-en-1-one 1-(4-(2-((4-chloro-2-hydroxy-5-iodophenyl)aMino)acetyl)piperazin-1-yl)prop-2-en-1-one 1469337-95-8 C15H17ClIN3O3
K-Ras(G12C) inhibitor 6 K-Ras(G12C) inhibitor 6 2060530-16-5 C17H22Cl2N2O3S
NSC 23766 (hydrochloride) NSC 23766 (hydrochloride) 1177865-17-6 C24H35N7
P276 P276 920113-03-7 C21H21Cl2NO5
K-Ras(G12C) inhibitor 9 K-Ras(G12C) inhibitor 9 1469337-91-4 C16H21ClIN3O4S
NU 6027 NU 6027 220036-08-8 C11H17N5O2
CCG-1423 CCG-1423 285986-88-1 C18H13ClF6N2O3
MK8745 MK8745 885325-71-3 C20H19ClFN5OS
ML167 ML167 1285702-20-6 C19H17N3O3
ML 141 ML 141 71203-35-5 C22H21N3O3S
SBE 13 hydrochloride SBE 13 hydrochloride 1052532-15-6 C24H28Cl2N2O4
K-Ras inhibitor K-Ras inhibitor 1469338-01-9 C20H30ClN3O2S3
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