KRAS Reducer Suppresses Pancreatic Cancer Malignancy


SW1 is an ADAM9 inhibitor that can promote KRAS protein degradation and enhances the efficacy of gemcitabine in pancreatic cancer treatment

BMCC Targeted indication

Pancreatic ductal adenocarcinoma

BMCC Status

Pre-clinical studies

BMCC Key features
  • High anti-KRAS activity efficacy
  • Small compound with a stable pharmacokinetic profile
  • Favorable safety profile with no side effects
BMCC Market

Use of anti-KRAS therapy, including reducing KRAS protein and activity in pancreatic cancer treatment. Importantly, SW1 with a very high safety profile can potentially synergize with clinical-used gemcitabine to block KRAS signaling in KRAS wild-type and mutants.

Furthermore, SW1 exhibits a stable pharmacokinetic profile in preclinical studies.


Current understandings of ADAM9 function in tumorigenesis are (1) inducing NK-related immune evasion, (2) increasing extrinsic RTK signals, and (3) stabilizing all KRASwt/mt proteins. SW1, a novel selective ADAM9 inhibitor, blocks ADAM9 activity and reduces its protein  amount  which  has  the  benefits  to  disrupt  known  regulation  mechanisms  of tumorigenesis. Moreover, SW1 enhances the chemosensitivity in vivo models.


in vitro efficacy

˙ SW1 is a specific ADAM9 inhibitor targeting its protease function and reducing its protein amounts

˙ SW1 broadly reduces KRAS proteins in KRAS wild-type and mutants

˙ A combination of SW1 and gemcitabine shows potent anti-cancer effects

in vivo efficacy

˙ SW1 suppresses tumor growth and prolongs survival in the KrasG12D spontaneous pancreatic cancer model

˙ The combination of SW1 and gemcitabine suppresses tumor growth and prolongs survival in the syngeneic pancreatic cancer model

˙ Potent efficacy of the combination of SW1 and gemcitabine in the patient-derived cell xenograft model (CR:70%; PR:20%; SD: 10%)

Safety pharmacology and general toxicology

Mice are tolerant in the 2-month daily treatment of SW1 without any blood cell count change or liver/kidney damage.

Pharmaceutical development

SW1 is very stable on the physical and chemical properties at weeks under acceleration conditions.


Two Taiwan patents (2020, 2021) and one US patent (2022) have been granted; the individual country patents in US, China, and Europe are in pending


Theranostics 11(8):3661-3675. January 26, 2021
Cancer Research 74(18):5229-43. September 2014


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