S-Tritylcysteine

Names

[ Name ]:
S-Tritylcysteine

[Synonym ]:
S-Triphenylmethyl-L-cysteine
EG5 INHIBITOR II
Cys(Trt)-OH
3-tritylthio-L-alanine
Alanine, 3- (tritylthio)-, D-
L-Cys(trt)-OH
DL-Cysteine, S-(triphenylmethyl)-
L-CYSTEINE, S-(TRIPHENYLMETHYL)-
EINECS 218-195-8
S-Tritylcysteine
(R)-S-Tritylcysteine
(2S)-2-Ammonio-3-(tritylsulfanyl)propanoate
Cysteine, S-(triphenylmethyl)-
D-Cysteine, S- (triphenylmethyl)-
S-Trt-L-Lys-OH
H-Cys(Trt)-OH
L-Cysteine, S- (triphenylmethyl)-
TRITYL-L-CYSTEINE
H-L-Cys(Trt)-OH
MFCD00002611
CYSTEINE(TRT)-OH
Alanine, 3- (tritylthio)-, L-
Tritylthioalanine
Ethanaminium, 1-carboxy-2-[(triphenylmethyl)thio]-, inner salt, (1S)-

Biological Activity

[Description]:

S-Trityl-L-cysteine (NSC 83265) is a selective and allosteric kinesin Eg5 inhibitor with an IC50 of 1 μM for the inhibition of basal ATPase activity and 140 nM for the microtubule-activated ATPase activity. S-Trityl-L-cysteine has antitumor activities[1][2].

[Related Catalog]:

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> Kinesin

Signaling Pathways >> Cytoskeleton >> Kinesin

[Target]

Eg5

[In Vitro]

S-Trityl-L-cysteine binds to a unique pocket in the Eg5 motor domain formed by secondary structural elements (helix a2/loop L5/helix a3)[1]. S-Trityl-L-cysteine (1-20 µM; for 72 h) could mediate cell apoptosis, as well as cell cycle arrest, in a dose-dependent manner. S-Trityl-L-cysteine-mediated apoptosis and cell cycle arrest were triggered by activation of the mitogen-activated protein kinase and nuclear factor kB signaling pathways[1]. S-Trityl-L-cysteine induces mitotic arrest in HeLa cells (IC50 of 700 nM) with characteristic monoastral spindles[2].

[References]

[1]. Wei Wu, et al. S-trityl-L-cysteine, a novel Eg5 inhibitor, is a potent chemotherapeutic strategy in neuroblastoma. Oncol Lett. 2018 Jul;16(1):1023-1030.

[2]. Salvatore DeBonis, et al. In vitro screening for inhibitors of the human mitotic kinesin Eg5 with antimitotic and antitumor activities. Mol Cancer Ther. 2004 Sep;3(9):1079-90.

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
524.7±50.0 °C at 760 mmHg

[ Melting Point ]:
182-183 °C (dec.)(lit.)

[ Molecular Formula ]:
C₂₂H₂₁NO₂S

[ Molecular Weight ]:
363.47

[ Flash Point ]:
271.2±30.1 °C

[ Exact Mass ]:
363.129303

[ PSA ]:
88.62000

[ LogP ]:
5.56

[ Vapour Pressure ]:
0.0±1.4 mmHg at 25°C

[ Index of Refraction ]:
1.642

[ Storage condition ]:
-20°C

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: AY7710000

CHEMICAL NAME :: Alanine, 3-(tritylthio)-, L-

CAS REGISTRY NUMBER :: 2799-07-7

BEILSTEIN REFERENCE NO. :: 2339626

LAST UPDATED :: 199801

DATA ITEMS CITED :: 11

MOLECULAR FORMULA :: C22-H21-N-O2-S

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >540 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information. Volume(issue)/page/year: PB81-109993

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 45 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information. Volume(issue)/page/year: PB81-109993

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 936 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NCISP* National Cancer Institute Screening Program Data Summary, Developmental Therapeutics Program. (Bethesda, MD 20205) Volume(issue)/page/year: JAN1986

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 396 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NCISP* National Cancer Institute Screening Program Data Summary, Developmental Therapeutics Program. (Bethesda, MD 20205) Volume(issue)/page/year: JAN1986

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 59460 ug/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold

REFERENCE :: NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information. Volume(issue)/page/year: PB288-358

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 750 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea Gastrointestinal - nausea or vomiting

REFERENCE :: NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information. Volume(issue)/page/year: PB81-109993

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 150 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea Gastrointestinal - nausea or vomiting

REFERENCE :: NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information. Volume(issue)/page/year: PB81-109993

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 100 mg/kg

TOXIC EFFECTS :: Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Liver - jaundice, other or unclassified Blood - hemorrhage

REFERENCE :: TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 29,95,1974 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 250 mg/kg/5D-I

TOXIC EFFECTS :: Cardiac - pulse rate Lungs, Thorax, or Respiration - dyspnea Related to Chronic Data - death

REFERENCE :: NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information. Volume(issue)/page/year: PB216-419

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 375 mg/kg/33D-I

TOXIC EFFECTS :: Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases Related to Chronic Data - death

REFERENCE :: NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information. Volume(issue)/page/year: PB216-419

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 250 mg/kg/5D-I

TOXIC EFFECTS :: Liver - other changes Kidney, Ureter, Bladder - other changes Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

REFERENCE :: NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information. Volume(issue)/page/year: PB216-419

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xn:Harmful;

[ Risk Phrases ]:
R22

[ Safety Phrases ]:
S22-S24/25

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
AY7710000

[ HS Code ]:
2930909090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2930909090

[ Summary ]:
2930909090. other organo-sulphur compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%

Articles

Cdk1 phosphorylates the Rac activator Tiam1 to activate centrosomal Pak and promote mitotic spindle formation.

Nat. Commun. 6 , 7437, (2015)

Centrosome separation is critical for bipolar spindle formation and the accurate segregation of chromosomes during mammalian cell mitosis. Kinesin-5 (Eg5) is a microtubule motor essential for centroso...

Structure-activity relationship of S-trityl-L-cysteine analogues as inhibitors of the human mitotic kinesin Eg5.

J. Med. Chem. 51 , 1115-25, (2008)

The human kinesin Eg5 is a potential drug target for cancer chemotherapy. Eg5 specific inhibitors cause cells to block in mitosis with a characteristic monoastral spindle phenotype. Prolonged metaphas...

Dynamics of Human Telomerase Holoenzyme Assembly and Subunit Exchange across the Cell Cycle.

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Human telomerase acts on telomeres during the genome synthesis phase of the cell cycle, accompanied by its concentration in Cajal bodies and transient colocalization with telomeres. Whether the regula...