ネララビン

Slightly soluble to soluble in water

1.39e+01 g/L

209-217 °C (with decomposition)

209 - 217 °C (decomposition)

Danger

H302 (16.7%): Harmful if swallowed [Warning Acute toxicity, oral]；H315 (16.7%): Causes skin irritation [Warning Skin corrosion/irritation]；H319 (16.7%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]；H335 (16.7%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]；H341 (66.7%): Suspected of causing genetic defects [Warning Germ cell mutagenicity]；H351 (50%): Suspected of causing cancer [Warning Carcinogenicity]；H360 (16.7%): May damage fertility or the unborn child [Danger Reproductive toxicity]；H361 (50%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]；H361fd (33.3%): Suspected of damaging fertility; Suspected of damaging the unborn child [Warning Reproductive toxicity]；H372 (66.7%): Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]；H413 (33.3%): May cause long lasting harmful effects to aquatic life [Hazardous to the aquatic environment, long-term hazard]

P203, P260, P261, P264, P264+P265, P270, P271, P273, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 6 reports by companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

L01BB07

L - Antineoplastic and immunomodulating agents；L01 - Antineoplastic agents；L01B - Antimetabolites；L01BB - Purine analogues；L01BB07 - Nelarabine

QL - Antineoplastic and immunomodulating agents；QL01 - Antineoplastic agents；QL01B - Antimetabolites；QL01BB - Purine analogues；QL01BB07 - Nelarabine

Nelarabine is a prodrug of the cytotoxic deoxyguanosine analogue 9-ß-D-arabinofuranosylguanine (ara-G). Nelarabine is demethylated by adenosine deaminase (ADA) to ara-G. Ara-G is then transported into cells, where it undergoes three phosphorylation steps, resulting in the formation of ara-G triphosphate (ara-GTP). In the first phosphorylation step, ara-G is converted to ara-G monophosphate (ara-GMP). Ara-GMP is then monophosphorylated by deoxyguanosine kinase and deoxycytidine kinase to ara-G diphosphate, and then subsequently to the active ara-G triphosphate (ara-GTP). Ara-GTP is the one that exerts the pharmacological effect. Pre-clinical studies have demonstrated that targeted T-cells possess marked sensitivity to the agent. Since T lymphoblasts have a higher expression of deoxycytidine kinase, ara-G preferentially accumulates in T cells over B cells, thus showing higher toxicity to T lymphoblasts.[A2331,AA2334,A2335]

Once nelarabine is metabolized into ara-GTP, the metabolite accumulates in leukemic blasts and incorporates into DNA to exert its S phase-specific cytotoxic effects, leading to the induction of fragmentation and apoptosis. As a nucleoside analog, Ara-GTP competes with endogenous deoxyGTP (dGTP) for incorporation into DNA. Due to its intact 3'-OH group, ara-GTP can be incorporated into the growing DNA strand without absolute chain termination. Despite that, the inclusion of ara-GTP into DNA strand can impair proper DNA repair processes, although the exact mechanism is not well understood, leading to inhibition of DNA elongation, apoptosis, and cellular destruction. Additional cytotoxic activities may exist, but these are not fully understood.