ARS-1620: Kanseri nshya ya KRAS-mutant

Nk’uko ubushakashatsi bwasohotse muriAkagari,abashakashatsi bakoze inzitizi yihariye ya KRASG12C yitwa ARS-1602 itera kubyimba ibibyimba mu mbeba.

Umwanditsi mukuru, Matthew R Janes, PhD, ukomoka mu gace ka Wellspring Biosciences yagize ati: "Ubu bushakashatsi butanga ibimenyetso byerekana ko mutant KRAS ishobora kwibasirwa, kandi ikagaragaza ko ARS-1620 ihagarariye igisekuru gishya cy’imiti yihariye ya KRASG12C ifite ubushobozi bwo kuvura." San Diego, CA, na bagenzi be.

Guhinduka kwa KRAS ni oncogene ihindagurika cyane kandi ubushakashatsi bwibanze bwerekanye ko hafi 30% yibibyimba birimo ihinduka rya RAS. Ihinduka ryihariye rya KRAS ryiganje mubwoko bwihariye bwibibyimba. Kurugero KRASG12C ni ihinduka ryiganje muri kanseri y'ibihaha itari ntoya (NSCLC), kandi iboneka no muri adenocarcinoma pancreatic na colorectal.

Nubwo ubwiganze bwimyaka myinshi nubushakashatsi bwerekana mutant KRAS nkumushoferi nyamukuru wa tumorigenez no kurwanya ivuriro, mutant KRAS yabaye intagondwa.

Ingamba zinyuranye zagerageje kumenya molekile ntoya yibasira KRAS, ariko zavuyemo guhagarika KRAS mu tugari. Ibi byashishikarije abanditsi gushushanya urwego rwo kunoza imiterere yihariye ya KRAS, harimo nu mufuka wa 2 (S-IIP) KRASG12C inhibitor ihuza kandi ikora hamwe na leta ya KRAS igana na GDP, ikayifata muburyo budahinduka.

Kugirango bigire umumaro, inhibitor igomba kugira imbaraga nyinshi kandi byihuse guhuza kinetics. Igomba kandi kuba ifite imiti myiza ya farumasi kugirango ikomeze kandi imare igihe kinini kugirango ifate leta idakora ya KRAS idakora nucleotide yihuta.

Abashakashatsi bakoze igishushanyo mbonera cya ARS-1620 hamwe n’ibintu bisa n’ibiyobyabwenge, banongerera imbaraga imbaraga zo mu gisekuru cya mbere. Gukora neza hamwe na kinetics kumurongo wa selile hamwe na mutant allele noneho byasuzumwe kugirango hamenyekane niba intego yo kubuza KRAS-GTP mubyimba yari ihagije.

Kubuza gukura kwakagari, kimwe nibishoboka ko habaho ibisubizo bidasanzwe bishobora kwerekana ubushobozi bwuburozi, byasuzumwe.

Hanyuma, gusuzuma intego yibikorwa muri vivo, umunwa ARS-1620 wahawe imbeba zifite imiterere ya xenograft yerekana imiterere ya KRAS p.G12C nkumuti umwe, cyangwa buri munsi muminsi 5.

Abashakashatsi bavuze ko ARS-1620 yabujije cyane gukura kw'ibibyimba mu buryo bukabije kandi bushingiye ku gihe hamwe no gusubira inyuma kw'ibibyimba.

Muri moderi eshanu zerekana amashusho yumurongo wa NSCLC mumbeba, moderi zose zashubije nyuma yibyumweru bibiri cyangwa bitatu byo kuvurwa, kandi bane muri batanu bagaragaje guhagarika cyane gukura kwikibyimba. Byongeye kandi, ARS-1620 yihanganiye neza nta burozi bw’amavuriro bwagaragaye mu gihe cyo kuvura.

Abanditsi bagize bati: "Hamwe na hamwe, ibimenyetso bya vivo byerekana ko ARS-1620 ikora neza nkumukozi umwe murwego rwa NSCLC itanga gihamya yerekana ko igice kinini cy’abarwayi bafite ihindagurika rya p.G12C KRAS bashobora kugirira akamaro imiti ivura KRASG12C".

Bongeyeho ko ARS-1620 ari intungamubiri ya KRASG12C itaziguye ya molekile inhibitor ifite imbaraga, ihitamo, bioavailable yo mu kanwa, kandi yihanganira neza.