[and how about test them via boltz or k-dense!!]
Rentosertib (formerly ISM001-055 / INS018_055) is the main drug Alex Zhavoronkov (founder and CEO of Insilico Medicine) is most likely referring to.
Key Details on Rentosertib
- What it is: A first-in-class small-molecule TNIK inhibitor (targets Traf2- and Nck-interacting kinase).
- How it was “found”: Both the novel target (TNIK) and the molecule itself were discovered and designed end-to-end using Insilico’s generative AI platform (PandaOmics for target identification from aging/fibrosis data + Chemistry42 for molecule design). This was one of the first (if not the first) fully AI-driven drug programs to reach clinical proof-of-concept.
- Primary development: For idiopathic pulmonary fibrosis (IPF) — a progressive, age-related lung scarring disease with high unmet need. It has completed a positive Phase IIa trial (published in Nature Medicine in 2025), showing good safety/tolerability, favorable pharmacokinetics, and dose-dependent improvements in lung function (e.g., forced vital capacity). Phase III trials were initiated around mid-2026, and an inhalation formulation is also advancing.
Geroprotective / Anti-Aging Angle
This is the key part tying into Zhavoronkov’s post. Separate research (using Insilico’s AI-driven robotics lab) showed that pharmacological TNIK inhibition with this compound acts as a senomorphic agent:
- It reduces markers of cellular senescence (a core hallmark of aging).
- It suppresses the senescence-associated secretory phenotype (SASP) and related inflammatory/fibrotic signals.
- Effects were seen in multiple senescence models without harming healthy cell viability.
IPF itself is strongly linked to aging biology (fibrosis, inflammation, senescence, extracellular matrix changes), so the drug was partly chosen because TNIK is implicated in both fibrosis and aging pathways. Insilico often starts target discovery from aging/longevity datasets.
Zhavoronkov and the company view these as potentially stronger/more direct geroprotective interventions than current options like GLP-1 agonists (semaglutide/tirzepatide), which mainly work through metabolic/weight-loss pathways (with some emerging but indirect longevity signals).
Broader Context: Insilico’s Pipeline
Insilico has a large internal pipeline of 30–40+ AI-discovered programs (many wholly owned), targeting:
- Fibrosis (lung, kidney, etc.)
- Various cancers
- Inflammation/immunology
- Other age-related conditions
Examples include PHD inhibitors (e.g., ISM5411 for IBD), NLRP3 inhibitors, and multiple oncology assets. Many targets were prioritized because they score highly on aging clocks or intersect with hallmarks of aging. The company’s explicit mission is extending healthy productive longevity via AI-accelerated drug discovery.
None of these are approved yet for general “anti-aging” or longevity use in healthy people (drugs are approved for specific diseases first, then potentially repurposed). Rentosertib is the most advanced and the one with the clearest published senomorphic/aging-related data so far.
In short: When Zhavoronkov says “my own drugs,” he’s talking about Insilico’s AI-designed pipeline — led by Rentosertib — which he hopes will deliver more potent, targeted effects on core aging biology (like senescence) compared to existing metabolic drugs. The company has been very public about this vision for years.
For the absolute latest trial updates, check Insilico’s site (insilico.com) or clinicaltrials.gov.
i think he mentioned Myricetin long ago
“GeroScope and shortlisted ten substances, all of which have lifespan-extending effects in animal models, and tested 6 of them for geroprotective effects in senescent human fibroblast cultures. PD-98059, a highly selective MEK1 inhibitor, showed both life-prolonging and rejuvenating effects. Natural compounds like N-acetyl-L-cysteine, Myricetin and Epigallocatechin gallate”
his leads might be overly concentrated on senescence… [ive never found them central yet for younger people]
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Publicly disclosed as of July 2026, here’s the clean version: Insilico claims 40+ total programs, 31 preclinical candidates nominated since 2021, and 13 IND-approved pipelines, but it does not publicly name every internal molecule. Because apparently biotech pipelines must be part science, part fog machine.
(Insilico Medicine)
So this is all the publicly identifiable Insilico / Zhavoronkov pipeline I could pin down, split into named drugs and target-only/undisclosed-code programs.
Named or semi-named Insilico pipeline drugs
Drug / code Target Main indication area Public status / note Rentosertib / ISM001-055 TNIK Idiopathic pulmonary fibrosis, kidney fibrosis Lead “AI-discovered” fibrosis asset. Oral rentosertib has Phase IIa IPF data; inhaled rentosertib also has IND clearance in China. (Insilico Medicine) Garutadustat / ISM5411 PHD1/2 IBD, especially ulcerative colitis Gut-restricted PHD inhibitor; Phase IIa BETHESDA trial has started. (Insilico Medicine) ISM4808 PHD Anemia associated with chronic kidney disease A related PHD-program asset licensed to TaiGen for Greater China. (Insilico Medicine) ISM3312 3CLpro / Mpro COVID / pan-coronavirus antiviral Oral 3CLpro inhibitor; Insilico’s pipeline describes it as an orally available covalent irreversible coronavirus protease inhibitor. (Insilico Medicine) ISM3091 USP1 BRCA-mutant / HRD cancers Licensed to Exelixis as a small-molecule USP1 inhibitor for BRCA-mutated tumors. (Exelixis, Inc.) ISM8207 QPCTL Advanced solid tumors, lymphoma, immuno-oncology First-in-patient Phase I initiated; co-developed with Fosun. (EurekAlert!) MEN2312 / ISM5043 KAT6 ER+/HER2− breast cancer and other oncology indications Licensed to Menarini/Stemline; reported as having entered clinical development. (Insilico Medicine) MEN2501 / ISM9682 KIF18A Chromosomal-instability solid tumors First-in-patient Phase I reported by Menarini/Stemline; originally Insilico’s KIF18A inhibitor. (Insilico Medicine) ISM6331 pan-TEAD Solid tumors, Hippo/YAP/TEAD biology Global Phase I first patient reported. (Insilico Medicine) ISM3412 MAT2A MTAP-deleted tumors Global Phase I first patient reported. (Insilico Medicine) ISM5939 ENPP1 Solid tumors, PD-1-resistant / STING-pathway immuno-oncology angle ENPP1 is listed in the public pipeline; IPO materials identify ISM5939 as the ENPP1 candidate. (Insilico Medicine) ISM8969 NLRP3 Parkinson’s disease / neuroinflammation; inflammatory diseases Brain-penetrant oral NLRP3 inhibitor; FDA IND approved, Phase I planned. (Insilico Medicine) ISM5059 NLRP3 Systemic inflammatory, autoimmune, metabolic, CV, ophthalmology indications Peripheral-restricted NLRP3 inhibitor, distinct from ISM8969; nominated as PCC. (Insilico Medicine) ISM3830 CBLB Advanced tumors / immunotherapy CBLB inhibitor nominated as PCC; IND-enabling initiated. (Insilico Medicine) ISM0676 GIPR antagonist Obesity, type 2 diabetes, obesity-associated CV disease PCC for metabolic disease; Insilico reports strong weight-loss data in combo with semaglutide in preclinical work. (Insilico Medicine) ISM6166 pan-KRAS KRAS-aberrant solid tumors Preclinical pan-KRAS inhibitor program disclosed in 2025 results / AACR materials. (Insilico Medicine) ISM6200 NR3C1 / glucocorticoid receptor Ovarian cancer, Cushing’s, hypercortisolism-related obesity, glaucoma PCC announced April 2026. (Insilico Medicine) ISM6210 CDK4 HR+/HER2− breast cancer Selective CDK4 inhibitor disclosed in AACR 2026 preclinical portfolio. (Insilico Medicine) ISM1745 MTA-cooperative PRMT5 MTAP-deleted cancers Preclinical oncology program disclosed in AACR 2026 materials. (Insilico Medicine) Public target programs where the exact active drug code is unclear or undisclosed
These are still on Insilico’s public pipeline / portfolio, but the company does not always give a stable public code. Very considerate of them. Naturally, humans must now maintain a spreadsheet like medieval monks.
Program Target Main idea FGFR2/3 inhibitor program FGFR2/3 Dual inhibitor for FGFR2/3-driven solid tumors; public materials describe a covalent FGFR2/3 inhibitor program. (Insilico Medicine) DGKA inhibitor program DGKα / DGKA Immuno-oncology target, likely aimed at checkpoint-resistant tumors and T-cell suppression reversal. (Insilico Medicine) CDK12/13 inhibitor program CDK12/13 Oncology program around transcriptional stress / DNA repair vulnerability. (Insilico Medicine) WRN inhibitor program WRN helicase MSI-H / mismatch-repair-deficient cancer synthetic-lethality play. (Insilico Medicine) Oral GLP-1R agonist programs GLP-1R Small-molecule GLP-1 receptor agonists for obesity/metabolic disease; Insilico has described once-weekly and broader oral GLP-1R work. (Insilico Medicine) DACRA program Dual amylin / calcitonin receptor agonist Metabolic/obesity program, basically chasing the post-GLP-1 obesity-drug gold rush because biology has become a subscription economy. (Insilico Medicine) APJ agonist program APJ / apelin receptor Cardiometabolic program using a biased agonist approach. (Insilico Medicine) Lp(a)-lowering molecule Lp(a) biology Lipoprotein(a) lowering program in the cardiometabolic portfolio. (Insilico Medicine) Nav1.8 pain program Nav1.8 Non-opioid acute/chronic pain program listed in offering materials. (HKEX News) Undisclosed kinase pain program Undisclosed kinase Non-opioid pain-management program listed in offering materials. (HKEX News) Undisclosed tumor-cell-proliferation program Undisclosed Solid-tumor oncology program listed in offering materials. (HKEX News) The actually useful compression
The pipeline clusters into a few big bets:
Fibrosis / inflammation: TNIK, PHD, NLRP3.
Oncology synthetic lethality / transcription / repair: USP1, MAT2A, PRMT5, WRN, CDK12/13, KAT6, KIF18A.
Tumor immunity: QPCTL, ENPP1, CBLB, DGKA, TEAD.
Metabolic / obesity / cardiometabolic: GIPR, GLP-1R, DACRA, APJ, NR3C1, Lp(a).
Pain / neuro: Nav1.8, NLRP3 brain-penetrant ISM8969.The flagship remains Rentosertib / ISM001-055, because it is the one Insilico keeps using as the proof-of-concept that its AI stack can go from target discovery to clinical-stage molecule rather than just generating glossy conference slides, humanity’s most overfunded art form.
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Tech tree rebalance