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Insilico Medicine Unveils ISM9528, a Preclinical Non-Opioid Candidate Showing Superior Pain Relief to Morphine
On 23 July 2026, Insilico Medicine announced that its latest preclinical drug candidate, ISM9528, has outperformed both morphine and pregabalin in animal pain models while maintaining a favorable safety profile. The orally available, brain‑penetrant compound targets a newly identified biological mechanism, Target Z, and marks the company’s 31st pre‑clinical candidate (PCC) generated since 2021.
The breakthrough follows the company’s use of its PandaOmics artificial intelligence platform to flag Target Z—a protein previously unlinked to pain management. By mining vast omics, textual and multimodal datasets, PandaOmics highlighted the target’s high expression in pain‑related cell types. Bioinformatics validation in both human and animal data confirmed this pattern, prompting laboratory investigation. Insilico then leveraged its Chemistry42 generative chemistry platform to optimise molecules for brain penetration, efficacy and safety, ultimately selecting ISM9528 as the lead compound.
In preclinical studies, ISM9528 produced dose‑dependent relief of mechanical allodynia in a spinal nerve ligation rat model of neuropathic pain. The middle dose yielded analgesic effects comparable to pregabalin for up to six hours post‑dosing. In a separate postsurgical pain model, the compound delivered rapid pain relief within 30 minutes, outperforming an equivalent dose of pregabalin. ISM9528 also demonstrated rapid systemic absorption and strong blood‑brain barrier permeability, reinforcing its pharmacokinetic profile.
According to the company, ISM9528 displayed a favourable safety profile in both in‑vitro and in‑vivo testing. Insilico said the compound’s safety characteristics, coupled with its efficacy, make it a promising candidate for advancing to human clinical studies, with first‑in‑human trials slated for 2027.
Insilico’s CEO and founder Dr Alex Zhavoronkov remarked, “To see a non‑opioid candidate outperform morphine in preclinical models is an unprecedented milestone, perhaps one of the most remarkable and unexpected results in our company’s history, a result of frontier AI, human ingenuity and scientific serendipity.” He added that the AI‑driven approach has accelerated target discovery for complex conditions like chronic pain, a disease that affects more than one in five people worldwide and is currently managed largely with opioids and non‑steroidal anti‑inflammatory drugs.
Dr Feng Ren, Co‑CEO and CSO, noted that ISM9528’s novel mechanism of action and distinct chemical structure deliver superior efficacy and a favourable safety profile. He highlighted that 13 of Insilico’s 31 PCCs have already received Investigational New Drug (IND) approval or clearance, underscoring the speed with which the platform is advancing programmes toward clinical testing.
The company pointed out that conventional early‑stage drug discovery typically takes between two‑and‑a‑half and four years, whereas its AI‑enabled pipeline has consistently progressed programmes from target identification to PCC nomination within 12 to 18 months.
Insilico’s strategy combines large‑scale data analysis, deep learning and generative chemistry. PandaOmics scans thousands of biological datasets to prioritise novel targets, while Chemistry42 designs molecules that meet multiple criteria, including brain penetration and synthetic accessibility. The goal is to shorten the medicinal chemistry cycle and bring new therapies to patients more rapidly.
ISM9528’s development arrives amid growing demand for alternative pain therapies. Chronic pain is estimated to affect more than 20 % of the global population, and current standards of care are limited by addiction risk, gastrointestinal toxicity and inconsistent efficacy. A non‑opioid therapy that can match or surpass morphine’s analgesic effect could address a significant unmet medical need.
Insilico Medicine’s next steps include preparing for human clinical trials, with the first studies slated for 2027. The company will also continue to refine its AI platforms and expand its pipeline of preclinical candidates.
The announcement underscores the potential of generative AI to accelerate drug discovery, but the transition from preclinical success to approved therapy remains a complex process that will require rigorous clinical evaluation.
The breakthrough follows the company’s use of its PandaOmics artificial intelligence platform to flag Target Z—a protein previously unlinked to pain management. By mining vast omics, textual and multimodal datasets, PandaOmics highlighted the target’s high expression in pain‑related cell types. Bioinformatics validation in both human and animal data confirmed this pattern, prompting laboratory investigation. Insilico then leveraged its Chemistry42 generative chemistry platform to optimise molecules for brain penetration, efficacy and safety, ultimately selecting ISM9528 as the lead compound.
In preclinical studies, ISM9528 produced dose‑dependent relief of mechanical allodynia in a spinal nerve ligation rat model of neuropathic pain. The middle dose yielded analgesic effects comparable to pregabalin for up to six hours post‑dosing. In a separate postsurgical pain model, the compound delivered rapid pain relief within 30 minutes, outperforming an equivalent dose of pregabalin. ISM9528 also demonstrated rapid systemic absorption and strong blood‑brain barrier permeability, reinforcing its pharmacokinetic profile.
According to the company, ISM9528 displayed a favourable safety profile in both in‑vitro and in‑vivo testing. Insilico said the compound’s safety characteristics, coupled with its efficacy, make it a promising candidate for advancing to human clinical studies, with first‑in‑human trials slated for 2027.
Insilico’s CEO and founder Dr Alex Zhavoronkov remarked, “To see a non‑opioid candidate outperform morphine in preclinical models is an unprecedented milestone, perhaps one of the most remarkable and unexpected results in our company’s history, a result of frontier AI, human ingenuity and scientific serendipity.” He added that the AI‑driven approach has accelerated target discovery for complex conditions like chronic pain, a disease that affects more than one in five people worldwide and is currently managed largely with opioids and non‑steroidal anti‑inflammatory drugs.
Dr Feng Ren, Co‑CEO and CSO, noted that ISM9528’s novel mechanism of action and distinct chemical structure deliver superior efficacy and a favourable safety profile. He highlighted that 13 of Insilico’s 31 PCCs have already received Investigational New Drug (IND) approval or clearance, underscoring the speed with which the platform is advancing programmes toward clinical testing.
The company pointed out that conventional early‑stage drug discovery typically takes between two‑and‑a‑half and four years, whereas its AI‑enabled pipeline has consistently progressed programmes from target identification to PCC nomination within 12 to 18 months.
Insilico’s strategy combines large‑scale data analysis, deep learning and generative chemistry. PandaOmics scans thousands of biological datasets to prioritise novel targets, while Chemistry42 designs molecules that meet multiple criteria, including brain penetration and synthetic accessibility. The goal is to shorten the medicinal chemistry cycle and bring new therapies to patients more rapidly.
ISM9528’s development arrives amid growing demand for alternative pain therapies. Chronic pain is estimated to affect more than 20 % of the global population, and current standards of care are limited by addiction risk, gastrointestinal toxicity and inconsistent efficacy. A non‑opioid therapy that can match or surpass morphine’s analgesic effect could address a significant unmet medical need.
Insilico Medicine’s next steps include preparing for human clinical trials, with the first studies slated for 2027. The company will also continue to refine its AI platforms and expand its pipeline of preclinical candidates.
The announcement underscores the potential of generative AI to accelerate drug discovery, but the transition from preclinical success to approved therapy remains a complex process that will require rigorous clinical evaluation.
