Lonidamine

Names

[ Name ]:
Lonidamine

[Synonym ]:
1-(2,4-Dichlorobenzyl)-1H-indazole-3-carboxylic acid
1H-Indazole-3-carboxylic acid, 1-[(2,4-dichlorophenyl)methyl]-
DICA
Lonidaminum
Lonidamin
Lonidaminum [INN-Latin]
MFCD00866285
Diclondazolic acid
Lonidamine
EINECS 256-510-0
1-[(2,4-dichlorophenyl)methyl]indazole-3-carboxylic acid
1-[(2,4-dichlorophenyl)methyl]-1H-indazole-3-carboxylic acid
Lonidamina
1-(2,4-Dichlorobenzyl)-1H-indazole-3-carboxylic acid Diclondazolic acid
Doridamina

Biological Activity

[Description]:

Lonidamine is an orally administered small molecule hexokinase inactivator.Target: OthersLonidamine is a derivative of indazole-3-carboxylic acid, which for a long time, has been known to inhibit aerobic glycolysis in cancer cells. It seems to enhance aerobic glycolysis in normal cells, but suppress glycolysis in cancer cells. This is most likely through the inhibition of the mitochondrially bound hexokinase. Later studies in Ehrlich ascites tumor cells showed that lonidamine inhibits both respiration and glycolysis leading to a decrease in cellular ATP. Clinical trials of lonidamine in combination with other anticancer agents for a variety of cancers has begun. Lonidamine has been used in the treatment of brain tumours in combination with radiotherapy and temozolomide. Results showed that a combination of temozolomide and lonidamine at clinically achievable, low plasma concentrations, could inhibit tumour growth, and lonidamine could reduce the dose of temozolomide required for radiosensitization of brain tumours. From Wikipedia.

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> Hexokinase

Research Areas >> Cancer

[References]

[1]. http://en.wikipedia.org/wiki/Lonidamine

[Related Small Molecules]

2-Deoxy-D-glucose | 3-Bromopyruvic acid

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Boiling Point ]:
537.9±45.0 °C at 760 mmHg

[ Melting Point ]:
207-209°C

[ Molecular Formula ]:
C₁₅H₁₀Cl₂N₂O₂

[ Molecular Weight ]:
321.158

[ Flash Point ]:
279.1±28.7 °C

[ Exact Mass ]:
320.011932

[ PSA ]:
55.12000

[ LogP ]:
4.32

[ Vapour Pressure ]:
0.0±1.5 mmHg at 25°C

[ Index of Refraction ]:
1.678

[ Storage condition ]:
Store at RT

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: NK7886000

CHEMICAL NAME :: 1H-Indazole-3-carboxylic acid, 1-(2,4-dichlorobenzyl)-

CAS REGISTRY NUMBER :: 50264-69-2

BEILSTEIN REFERENCE NO. :: 0894483

LAST UPDATED :: 199612

DATA ITEMS CITED :: 16

MOLECULAR FORMULA :: C15-H10-Cl2-N2-O2

MOLECULAR WEIGHT :: 321.17

WISWESSER LINE NOTATION :: T56 BNNJ B1R BG DG& DVQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1700 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - lacrimation Sense Organs and Special Senses (Eye) - ptosis Behavioral - changes in motor activity (specific assay)

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 525 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - lacrimation Sense Organs and Special Senses (Eye) - ptosis Behavioral - changes in motor activity (specific assay)

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 900 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - lacrimation Sense Organs and Special Senses (Eye) - ptosis Behavioral - changes in motor activity (specific assay)

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 435 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - lacrimation Sense Organs and Special Senses (Eye) - ptosis Behavioral - changes in motor activity (specific assay)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 14560 mg/kg/2Y-C

TOXIC EFFECTS :: Related to Chronic Data - changes in testicular weight

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 3 gm/kg/30D-I

TOXIC EFFECTS :: Related to Chronic Data - changes in prostate weight Related to Chronic Data - changes in testicular weight

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 3200 mg/kg/28D-I

TOXIC EFFECTS :: Gastrointestinal - nausea or vomiting Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 35 mg/kg

SEX/DURATION :: male 1 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 350 mg/kg

SEX/DURATION :: female 6-15 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 175 mg/kg

SEX/DURATION :: female 6-15 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 90 mg/kg

SEX/DURATION :: female 6-15 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 100 mg/kg

SEX/DURATION :: male 1 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 250 mg/kg

SEX/DURATION :: male 5 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :: Sperm Morphology

MUTATION DATA

TEST SYSTEM :: Primate - monkey

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

REFERENCE :: JRPFA4 Journal of Reproduction and Fertility. (Biochemical Soc. Book Depot, POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1960- Volume(issue)/page/year: 52,275,1978

Safety Information

[ Symbol ]:

GHS07, GHS08

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H302-H351-H360

[ Precautionary Statements ]:
P201-P281-P308 + P313

[ Personal Protective Equipment ]:
Eyeshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges

[ Hazard Codes ]:
T:Toxic;

[ Risk Phrases ]:
R60;R22;R40

[ Safety Phrases ]:
S53-S22-S36/37/39-S45

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
NK7886000

[ HS Code ]:
2933990090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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