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A ligand for the target, a recruiter for an E3 ligase, and a cell that does the rest: the protein is tagged and destroyed rather than blocked. Cereblon is the ligase almost everything uses today. The corpus holds 15 degraders and molecular glues medicines: 6 approved, 5 in phase 3, 55 trials recruiting, 12 companies named. Every section below says which records it was read from.
From 1 record:PROTACs & molecular glues (targeted protein degradation)
Instead of blocking a protein, these drugs tag it for the cell's own garbage disposal, removing it entirely.
Bifunctional molecule recruits an E3 ubiquitin ligase (cereblon, VHL) to the target, causing ubiquitination and proteasomal destruction.
From 15 records:AZD9750BexobrutidegBGB-16673BMS-986365GolcadomideIberdomideInavolisibLenalidomideand 7 more in the JSON
Target against e3 ligase, 7 by 1. Open the grid, where every cell links to its medicines and the records behind its state.
From 6 records:ThalidomideLenalidomidePomalidomideInavolisibIberdomideVepdegestrant
Thalidomide Thalomid | IKZF1 (Ikaros) | 1998 | USEU | approved | ||
Lenalidomide Revlimid | IKZF1 x IKZF3 | 2005 | US | approved | ||
Pomalidomide Pomalyst / Imnovid | IKZF1 x IKZF3 | 2013 | USEU | approved | ||
Inavolisib Itovebi | PIK3CA / PI3K-alpha | 2024 | USEU | approved | ||
Iberdomide Zenbexus | IKZF1 x IKZF3 | 2026 | US | approved | ||
Vepdegestrant Veppanu | Estrogen receptor (ERα) | 2026 | US | approved |
From 5 records:BexobrutidegBGB-16673BMS-986365GolcadomideMezigdomide
| Phase 3 trials here | ||||||
|---|---|---|---|---|---|---|
| Bexobrutideg | BTK (Bruton tyrosine kinase) | 3 | phase 3 | |||
| BGB-16673 | BTK (Bruton tyrosine kinase) | 6 | phase 3 | |||
| BMS-986365 | Androgen receptor | 0 | phase 3 | |||
| Golcadomide | IKZF1 x IKZF3 | 6 | phase 3 | |||
| Mezigdomide | IKZF1 x IKZF3 | 7 | phase 3 |
From 15 records:AZD9750BexobrutidegBGB-16673BMS-986365GolcadomideIberdomideInavolisibLenalidomideand 7 more in the JSON
From 12 records:Bristol Myers SquibbNatco PharmaArvinasLupeng PharmaceuticalsPfizer (incl. Seagen)Roche / GenentechAstraZenecaBeOne Medicines (formerly BeiGene)and 4 more in the JSON
| Company | Type | Medicines | Approved | Phase 3 | Which |
|---|---|---|---|---|---|
| Bristol Myers Squibb US | pharma | 7 | 4 | 3 | |
| Natco Pharma IN | pharma | 2 | 2 | 0 | |
| Arvinas US | biotech | 1 | 1 | 0 | |
| Lupeng Pharmaceuticals CN | biotech | 1 | 1 | 0 | |
| Pfizer (incl. Seagen) US | pharma | 1 | 1 | 0 | |
| Roche / Genentech CH | pharma | 1 | 1 | 0 | |
| AstraZeneca GB | pharma | 1 | 0 | 0 | |
| BeOne Medicines (formerly BeiGene) CH | biotech | 1 | 0 | 1 | |
| Nurix Therapeutics US | biotech | 1 | 0 | 1 | |
| Qilu Pharmaceutical CN | pharma | 1 | 0 | 0 | |
| Ranok Therapeutics (Hangzhou) CN | biotech | 1 | 0 | 0 | |
| Triana Biomedicines US | biotech | 1 | 0 | 0 |
From 55 records:A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)A Study Comparing AZD0120, a Dual-targeted CAR-T Against B-cell Maturation Antigen (BCMA) and CD19, Versus Standard Regimens in Participants With RelaA Study Evaluating the Efficacy and Safety of Inavolisib Plus CDK4/6 Inhibitor and Letrozole vs Placebo + CDK4/6i and Letrozole in Participants With Endocrine-Sensitive PIK3CA-Mutated, Hormone Receptor-Positive, HER2-Negative Advanced Breast CancerA Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination TherapyA Study of Belantamab Mafodotin Administered in Combination With Lenalidomide and Dexamethasone (BRd) Versus Daratumumab, Lenalidomide, and DexamethasA Study of Teclistamab in Combination With Daratumumab and Lenalidomide (Tec-DR) and Talquetamab in Combination With Daratumumab and Lenalidomide (TalA Study of the Efficacy and Safety of BCD-248 in Combination With Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma (AMMADINA)A Study to Compare the Efficacy and Safety of Golcadomide in Combination With Rituximab (Golca + R) vs Investigator's Choice in Participants With Relaand 47 more in the JSON
From 1 record:Inavolisib
High blood sugar as a side effect of drugs that block the PI3K/AKT pathway, because the same pathway carries insulin's signal in muscle and liver. It is the main reason these otherwise effective breast cancer drugs are…
Linked fromInavolisib
From 5 records:PalbociclibRibociclibAbemaciclibElacestrantVepdegestrant
Hormone-positive breast cancer escapes either by mutating the oestrogen receptor so it no longer needs oestrogen, or by rewiring the cell-cycle engine (RB loss, cyclin E) so CDK4/6 no longer matters.
ExemplarsPalbociclibRibociclibAbemaciclibElacestrantVepdegestrant
From 19 records:PROTACs & molecular glues (targeted protein degradation)Cereblon E3 ligase modulators (CELMoDs)Molecular glue discovery platformsDegrader-antibody conjugate (DAC)AZD9750BexobrutidegBGB-16673BMS-986365and 11 more in the JSON
CEPHEUS: daratumumab quadruplet for newly diagnosed myeloma patients not having a transplant, with MRD-negativity as the main endpoint In patients who were transplant-ineligible or deferred transplant, the daratumumab quadruplet raised deep-remission rates from about 39% to… | 2,025 | Nature Medicine | rct | |
PERSEUS: daratumumab added to bortezomib-lenalidomide-dexamethasone around autologous transplant in newly diagnosed myeloma Adding daratumumab to the standard three-drug induction, transplant and maintenance cut progression or death by 58% and pushed MRD-negativi… | 2,024 | New England Journal of Medicine | rct | |
CARTITUDE-4: cilta-cel CAR-T versus standard combinations after one to three prior lines of myeloma therapy Moving BCMA CAR-T to the second line cut the risk of progression or death by 74% compared with standard triplets, and later improved overal… | 2,023 | New England Journal of Medicine | rct | |
E3A06: lenalidomide versus observation in smouldering multiple myeloma Lenalidomide alone delayed progression to active myeloma in people with intermediate- or high-risk smouldering disease, but side effects le… | 2,020 | Journal of Clinical Oncology | rct | |
AUGMENT: lenalidomide plus rituximab versus rituximab alone in relapsed indolent lymphoma Adding lenalidomide to rituximab more than doubled the time to progression in relapsed follicular and marginal zone lymphoma compared with… | 2,019 | Journal of Clinical Oncology | rct | |
CASSIOPEIA: daratumumab added to bortezomib, thalidomide and dexamethasone before and after transplant in newly diagnosed myeloma Adding the antibody daratumumab to a standard three-drug induction and consolidation around autologous transplant deepened responses and de… | 2,019 | The Lancet | rct | |
MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant Adding the CD38 antibody daratumumab to standard lenalidomide-dexamethasone cut the risk of progression or death by about 44% in older myel… | 2,019 | New England Journal of Medicine | rct | |
RELEVANCE: rituximab plus lenalidomide in advanced untreated follicular lymphoma A chemotherapy-free combination of rituximab and lenalidomide worked as well as rituximab with chemotherapy for untreated follicular lympho… | 2,018 | New England Journal of Medicine | rct | |
IFM 2009: lenalidomide, bortezomib and dexamethasone with or without upfront transplantation for myeloma Adding an early autologous stem cell transplant to modern three-drug therapy delayed relapse in newly diagnosed myeloma, though overall sur… | 2,017 | New England Journal of Medicine | rct | |
Veber 2002: molecular properties that influence the oral bioavailability of drug candidates An analysis of over a thousand experimental drug candidates that found molecules with few rotatable bonds and a modest polar surface area w… | 2,002 | Journal of Medicinal Chemistry | methods | |
The first PROTAC: a chimeric molecule that tags a protein for destruction Crews and Deshaies built a two-headed molecule linking a ligand for the target protein MetAP-2 to a peptide recognised by an E3 ubiquitin l… | 2,001 | PNAS | basic |
From 6 records:ADC roadmap: from Mylotarg to bispecific and dual-payload ADCsDrug discovery roadmap: screening in mice → maps of dependency → designing in silicoEpigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenomeHormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood testRadical oncology: what could change the war by 2035Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall
From 19 records:PROTACs & molecular glues (targeted protein degradation)Cereblon E3 ligase modulators (CELMoDs)Molecular glue discovery platformsDegrader-antibody conjugate (DAC)AZD9750BexobrutidegBGB-16673BMS-986365and 11 more in the JSON
MRD-guided treatment-free intervals in myeloma If a patient has had no detectable myeloma for a year or more, stop maintenance and watch, restarting only if disease reappears. | Being tested at scale | |
An open-science consortium on the undruggable drivers, open until a candidate Companies and public funders would pool money and scientists to crack the hardest cancer proteins, such as MYC and mutant p53, sharing everything openly until… | Early clinical | |
Attack the backup copy when a tumour has lost the original gene Tumours often lose one of a pair of near-identical genes. They then depend entirely on the remaining copy, which a drug can block, killing only the cancer. | Early clinical | |
BTK degraders to pre-empt resistance in frontline CLL If destroying BTK works when every inhibitor has failed, using it first might stop resistance from ever emerging. | Early clinical | |
Molecular-progression switching beyond ESR1 SERENA-6 showed you can act on a blood test before the scan changes. The same logic could apply to PIK3CA, AKT1, or HER2 mutations emerging on treatment. | Early clinical | |
An open degrader consortium against every undruggable driver transcription factor Cancer's most important drivers, such as MYC and mutant p53, cannot be blocked with normal drugs. Pool effort and share results openly to build molecules that… | Preclinical evidence | |
Degraders for the fusion proteins that drive childhood sarcomas Some sarcomas in children are caused by two genes fused into one abnormal protein. That protein is the whole disease, but no drug binds it. Destroying it inste… | Preclinical evidence | |
Design protein degraders small enough to get into the brain New drugs that destroy cancer proteins are usually too big to enter the brain. Making much smaller versions could bring this approach to brain tumours. | Preclinical evidence | |
Destroy the truncated androgen receptor that hormone drugs cannot touch In advanced prostate cancer the AR-V7 splice variant of the androgen receptor lacks the ligand-binding domain that enzalutamide and abiraterone act on, and its… | Preclinical evidence | |
Drag cancer's surface and secreted proteins to the cell's recycling bin Some cancer proteins sit on the cell surface or float outside cells, where protein-destroying drugs cannot reach. A different trick can drag them inside to be… | Preclinical evidence | |
Efflux-agnostic therapy for mesenchymal TNBC Some tumours pump out every drug. Use treatments the pumps cannot touch: radiation, radioligands, immune cells, and payloads designed to evade them. | Preclinical evidence | |
Find E3 ligases that only tumours have, and build degraders around them Protein-destroying drugs work by hijacking cellular waste-disposal machines. Using a machine that is mostly present in cancer cells would make these drugs safe… | Preclinical evidence | |
Molecular glues that break the MYC-MAX partnership MYC is a cancer-driving transcription factor with no drug because it has no binding pocket. A molecular glue or degrader that jams its required partner MAX, or… | Preclinical evidence | |
One-two punch: clear senescent cells after chemotherapy Chemotherapy leaves behind senescent cells that inflame tissues and help tumours relapse. A short course of senolytic drugs afterwards might reduce relapse and… | Preclinical evidence | |
Screen glue-like compounds against every cancer cell line and publish it Molecular glue degraders make one protein destroy another, but thalidomide analogues and indisulam were found by luck. A systematic screen of chemical librarie… | Preclinical evidence | |
Use antibodies to deliver protein-destroying drugs into the right cells Drugs that destroy proteins can hit healthy cells too. Attaching them to an antibody that only docks onto tumour cells would keep them where they are needed. | Preclinical evidence | |
Degrade the damaged p53 protein rather than trying to repair it Some faulty p53 proteins do not just stop protecting the cell; they actively help the cancer. Removing them entirely may be easier than fixing them. | Speculative | |
Instruct tumour cells to make antibodies against their own oncoprotein Deliver genetic instructions so the cancer cell itself manufactures a molecule that traps its driver protein inside the cell. | Speculative |
From no record yet:
API synthesis, tablets and sterile vials. The 2023 cisplatin and carboplatin shortage and the BCG shortage are the worked examples.
Small-molecule API synthesisOral solid dose manufacturing (tablets and capsules)Generic sterile injectables (the 2023 platinum shortage)Sterile fill-finish and lyophilisationBCG manufacturing and the bladder cancer BCG shortageGeneric oncology drug supply and shortage mitigationGMP, inspections, Form 483s and warning letters
CompaniesIntas Pharmaceuticals (Accord Healthcare)Teva PharmaceuticalsFresenius KabiPfizer (incl. Seagen)Hikma PharmaceuticalsAmneal PharmaceuticalsSun Pharmaceutical IndustriesDr. Reddy's LaboratoriesCiplaSandozViatrisCivica RxMerck & Co. (MSD)
The manufacturing map draws every site and the seven supply chains.
No manufacturing technology record is listed for this format.
The medicines are the ones the open drug engine files under degraders and molecular glues, whether it placed them on its grid or listed them as unresolved. The technology records are listed by hand (src/lib/modular-formats.ts) and each carries a pill back here. Everything else follows the graph's links from those two sets: approvals, cancers and toxicity from the medicine records; companies, trials, papers and ideas from the records that name a medicine or technology; roadmap steps from their refs; resistance from the atlas; manufacturing from the site and supply chain records.
Nothing here is written for the hub. Where the corpus holds no record for a section, the section says so rather than filling the gap, and the counts are counts of records in OnCo, not of the world. The JSON companion carries every section with the record ids behind it. Not medical advice.