Protein / target

Transforming growth factor beta-1 proprotein

Encoded byTGFB1P01137Homo sapiensSwiss-Prot

UniProt: P01137 Ensembl: ENSG00000105329 HGNC: HGNC:11766 NCBI Gene: 7040

Clinically validated

Therapeutic maturity

Approved medicines

Open Targets target-level

View by indication →

Clinical trials

Small-molecule tractable

Druggability

Structure with Ligand

Protein at a glance

Biological role

Type III transforming growth factor beta receptor binding

Strongest disease association

Cystic Fibrosis

Via encoding gene TGFB1 · Genetic evidence · score 0.57

Therapeutic position

Established drug target

Antibodies

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active subunit of TGF-beta-1, respectively

Subcellular location

Secreted, extracellular space, extracellular matrixSecreted

Domains and Gene Ontology detail (163)

Gene Ontology

Caxon
Cblood microparticle
Ccell surface
Ccytoplasm
Cextracellular matrix
Cextracellular region
Cextracellular space
CGolgi lumen
Cneuronal cell body
Cnucleus
Cplasma membrane
Cplatelet alpha granule lumen

390 aa · 44 kDa

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell migrationGOCell proliferation & survivalGOGrowth-factor signallingGOLipid & lipoprotein metabolismGOCell adhesionUniProt · GOImmune signallingGO

View supporting evidence

Cell migration

·negative regulation of blood vessel endothelial cell migration
·positive regulation of blood vessel endothelial cell migration
·positive regulation of cell migration
·positive regulation of chemotaxis

Cell proliferation & survival

·negative regulation of cell population proliferation
·positive regulation of cell population proliferation
·regulation of cell population proliferation

Growth-factor signalling

·cellular response to insulin-like growth factor stimulus
·positive regulation of epidermal growth factor receptor signaling pathway

Lipid & lipoprotein metabolism

·cellular response to low-density lipoprotein particle stimulus
·response to cholesterol

Cell adhesion

·Secreted, extracellular space, extracellular matrix
·extracellular matrix
·cell-cell junction organization
·extracellular matrix assembly

Immune signalling

·cytokine activity
·adaptive immune response based on somatic recombination of immune receptors built from i…
·connective tissue replacement involved in inflammatory response wound healing
·negative regulation of fat cell differentiation

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Approved medicines with mapped indications

1 medicine · 3 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Anemia1 medicine

luspatercept

beta-Thalassemia1 medicine

luspatercept

Myelodysplastic Syndromes1 medicine

luspatercept

Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

luspatercept

ApprovedInhibitor

Transforming growth factor beta inhibitor

Indicated for Anemia, beta-Thalassemia, Myelodysplastic Syndromes

Acts on a complex — shared with TGFB2, TGFB3 · 1 of 3 recorded protein targets — narrow recorded profile

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene TGFB1

Gene-level evidence surfaced through the gene TGFB1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Myelodysplastic syndrome

0.73Moderately supported

Clinical evidence dominant · Open Targets 0.58

Cystic Fibrosis

0.70Moderately supported

Genetic evidence dominant · Open Targets 0.45

Anemia

0.69Moderately supported

Clinical evidence dominant · Open Targets 0.55

beta-Thalassemia

0.59Moderately supported

Clinical evidence dominant · Open Targets 0.48

Neoplasms

0.43Preliminary

Pathway evidence dominant · Open Targets 0.53 · no direct causal or clinical evidence

View evidence synthesis (5)

Myelodysplastic syndromeModerately supported

0.73

agreement 0.57–0.88

Clinical84%Literature16%

Open Targets aggregate 0.58 · 2 independent evidence families

Cystic FibrosisModerately supported

0.70

agreement 0.58–0.82

Genetic62%Animal model22%Literature16%

Open Targets aggregate 0.45 · 3 independent evidence families

AnemiaModerately supported

0.69

agreement 0.53–0.84

Clinical87%Literature13%

Open Targets aggregate 0.55 · 2 independent evidence families

beta-ThalassemiaModerately supported

0.59

agreement 0.43–0.74

Clinical99%Literature1%

Open Targets aggregate 0.48 · 2 independent evidence families

NeoplasmsPreliminary

0.43

agreement 0.25–0.61

Pathway69%Literature31%

Open Targets aggregate 0.53 · 2 independent evidence families · no direct causal or clinical evidence

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Myelodysplastic syndrome0.58

Anemia0.55

Neoplasms0.53

beta-Thalassemia0.48

Cystic Fibrosis0.45

Drug development

5 compounds recorded · 1 approved · 4 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (5)

LUSPATERCEPTApproval

BINTRAFUSP ALFAPhase 3

FRESOLIMUMABPhase 2

METELIMUMABPhase 1 2

LY-2382770Phase 2

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand and med-quality pocket) — no clinical-stage drug of this modality recorded.

Antibodies — Strong

Advanced Clinical and UniProt loc high conf support this modality.

Protein degraders — Emerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

Other modalities — Strong

Approved Drug support this modality.

View underlying tractability evidence (11)

SM · Structure with LigandSM · Med-Quality PocketSM · Druggable FamilyAB · Advanced ClinicalAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule BinderOC · Approved Drug

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

regulation of transcription factor activityToxCastregulation of gene expressionToxCast

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

A Phase 4 Study to Evaluate Safety and Effectiveness of Luspatercept (ACE-536) for the Treatment of Anemia Due to IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) With Ring Sideroblasts Who Require Red Blood Cell Transfusions in Participants Who Have Had Unsatisfactory Response to or Are Ineligible to Erythropoietin Based Therapy and in Participants With Transfusion Dependent Anemia Due to Beta-ThalassemiaPHASE4

ACTIVE_NOT_RECRUITING · via luspatercept · NCT05891249

Luspatercept Versus Epoetin in Treating Poor Erythroid Engraftment for Hematological MalignanciesPHASE2/PHASE3

NOT_YET_RECRUITING · via luspatercept · NCT07636486

The Efficacy and Safety of Luspatercept in Preventing Poor Erythroid Engraftment After Allo-HSCT for Hematological Malignancies With Moderate to Severe Myelofibrosis: A Prospective, Multicenter, Randomized Controlled StudyPHASE2/PHASE3

NOT_YET_RECRUITING · via luspatercept · NCT07539779

Azacitidine Plus Luspatercept Versus Azacitidine Monotherapy in Higher-risk Myelodysplastic Neoplasms: a Randomized Prospective StudyPHASE3

NOT_YET_RECRUITING · via luspatercept · NCT06927232

View all trials (26)

A Phase 3, Open-label, Randomized Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) vs Epoetin Alfa for the Treatment of Anemia Due to Revised International Prognostic Scoring System (IPSS-R) Very Low, Low, or Intermediate-Risk Myelodysplastic Syndrome (MDS) in Erythropoiesis-Stimulating Agent (ESA)-Naive Participants Who Are Non-Transfusion Dependent (NTD): The "ELEMENT-MDS" TrialPHASE3

ACTIVE_NOT_RECRUITING · via luspatercept · NCT05949684

A Phase 3b, Open-label Study Evaluating the Efficacy and Safety of Luspatercept (BMS-986346/ACE-536) Initiated at Maximum Approved Dose in LR-MDS With IPSS-R Very Low-, Low-, or Intermediate-risk Who Require RBC Transfusions (MAXILUS)PHASE3

ACTIVE_NOT_RECRUITING · via luspatercept · NCT06045689

A Phase IIIb, Open-label, Single Arm Study to Evaluate the Efficacy and Safety of Luspatercept in Patients With Lower-risk MDS and Ring-sideroblastic Phenotype (MDS-RS)PHASE3

ACTIVE_NOT_RECRUITING · via luspatercept · NCT05181592

A Phase 3b, Open-label, Single-arm, Rollover Study to Evaluate Long-term Safety in Subjects Who Have Participated in Other Luspatercept (ACE-536) Clinical TrialsPHASE3

RECRUITING · via luspatercept · NCT04064060

A Phase 3, Open-label, Randomized Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) Versus Epoetin Alpha for the Treatment of Anemia Due to IPSS-R Very Low, Low or Intermediate Risk Due to Myelodysplastic Syndrome (MDS) in ESA Naïve Subjects Who Require Red Blood Cell TransfusionsPHASE3

ACTIVE_NOT_RECRUITING · via luspatercept · NCT03682536

A Phase II Study of Combination Therapy With Luspatercept in Lower Risk Myelodysplasia: A Tier 1 MyeloMATCH SubstudyPHASE2

NOT_YET_RECRUITING · via luspatercept · NCT07463820

A Clinical Study on the Efficacy and Safety of Luspatercept in Improving Early Anemia After Allogeneic Hematopoietic Stem Cell TransplantationPHASE2

NOT_YET_RECRUITING · via luspatercept · NCT07450313

A Phase II Study of Luspatercept Plus Darbepoetin Alfa in Non-mutated SF3B1 Lower-risk Myelodysplastic SyndromesPHASE2

RECRUITING · via luspatercept · NCT07096297

An Exploratory Study on the Safety and Efficacy of Luspatercept in the Treatment of Anemia Following Allogeneic Hematopoietic Stem Cell Transplantation for Acute LeukemiaPHASE1/PHASE2

RECRUITING · via luspatercept · NCT07362095

Efficacy of Luspatercept In Clonal Cytopenias of Uncertain SignificancePHASE2

RECRUITING · via luspatercept · NCT06788691

A Phase 2 Open-label Study to Evaluate Momelotinib in Combination With Luspatercept in Participants With Transfusion Dependent Primary or Secondary MyelofibrosisPHASE2

RECRUITING · via luspatercept · NCT06517875

Master Screening and Reassessment Protocol (MSRP) for the NCI MyeloMATCH Clinical TrialsPHASE2

RECRUITING · via luspatercept · NCT05564390

A Pilot, Open-Label Study of Luspatercept for Patients With Lower Risk Myelodysplastic Syndromes (MDS)PHASE2

ACTIVE_NOT_RECRUITING · via luspatercept · NCT06113302

Safety and Efficacy Study of the Tapering Dose of Luspatercept in Patients With Lower-risk Myelodysplastic SyndromesPHASE2

RECRUITING · via luspatercept · NCT05925504

A Phase 2, Single Arm Study of Luspatercept for the Treatment of Anemia in Lower Risk Myelodysplastic Syndromes (MDS) or Non-Proliferative Myelodysplastic Syndromes/ Myeloproliferative Neoplasms (MDS/MPN)PHASE2

ACTIVE_NOT_RECRUITING · via luspatercept · NCT05732961

A Phase 2, Study for the Treatment of Anemia With Alpha (α)-Thalassemia to Determine the Efficacy and Safety of Luspatercept (BMS-986346/ACE-536) in Adults and Evaluate the Safety and Pharmacokinetics in AdolescentsPHASE2

RECRUITING · via luspatercept · NCT05664737

Efficacy and Safety of Luspatercept for the Treatment of Anemia Due to Myelodysplastic Syndromes With del5q, Refractory/Resistant/Intolerant to Prior Treatments, Who Require Red Blood Cell TransfusionsPHASE2

RECRUITING · via luspatercept · NCT05924100

A Phase 2, Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Luspatercept (ACE-536) in Chinese Adult Subjects Who Require Regular Red Blood Cell Transfusions Due to Beta (β)-ThalassemiaPHASE2

ACTIVE_NOT_RECRUITING · via luspatercept · NCT05567458

A Phase II, Open-label, Single Arm Study to Evaluate the Efficacy of Luspatercept in Erythropoiesis-stimulating Agent Naive Lower-risk MDS Patients With or Without Ring Sideroblasts Who do Not Require RBC TransfusionsPHASE2

RECRUITING · via luspatercept · NCT05384691

A Randomized Phase I/ II Multicenter Study Evaluating Combination of Luspatercept in LR-MDS Without RS Having Failed or Being Ineligible to ESAPHASE1/PHASE2

RECRUITING · via luspatercept · NCT05181735

Treatment of Transfusion-dependent Nonsevere Aplastic Anemia With Luspatercept: a Multicenter Prospective Clinical StudyNA

NOT_YET_RECRUITING · via luspatercept · NCT06964971

A Randomized, Controlled Trial Comparing the Safety and Efficacy of Luspatercept Plus Cyclosporine Versus Cyclosporine Alone for the Treatment of Newly Diagnosed Non-transfusion-dependent Non-severe Aplastic Anemia (NSAA)PHASE4

WITHDRAWN · via luspatercept · NCT06424639

Roxadustat Combined With Luspatercept Versus Luspatercept Monotherapy in the Treatment of Refractory Myelodysplastic Syndrome With Ring Sideroblasts (MDS-RS): A Prospective Randomized Controlled StudyPHASE4

UNKNOWN · via luspatercept · NCT06006949

A Phase 3, Double-Blind, Placebo Controlled Multicenter Study to Determine the Efficacy and Safety of Luspatercept (ACE-536) in Adults With Transfusion Dependent Beta (B)-ThalassemiaPHASE3

COMPLETED · via luspatercept · NCT02604433

A Phase 3, Double-blind, Randomized Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) Versus Placebo for the Treatment of Anemia Due to the IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes in Subjects With Ring Sideroblasts Who Require Red Blood Cell Transfusions.PHASE3

COMPLETED · via luspatercept · NCT02631070

Phase II Study to Determine the Efficacy and Safety of Luspatercept (ACE-536) in Patients With Myelodysplastic/Myeloproliferative Neoplasms With Ring Sideroblasts and Thrombocytosis (MDS/MPN-RS-T) and Myelodysplastic/Myeloproliferative Neoplasms, Unclassifiable With Ring Sideroblasts (MDS/MPN-U With RS)PHASE2

TERMINATED · via luspatercept · NCT05005182

ClinicalTrials.gov via the drug-target graph.

What's happening now

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

Regulatory approval2020-06-25
Approval: Reblozyl (EMA)
ema · regulatory · ema · via luspatercept
New publication2020-01-21
Luspatercept in Myelodysplastic Syndromes: Who and When?
Hematology/oncology clinics of North America · 2020 · 11 citations · Europe PMC · via luspatercept
New publication2020-01-01
Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes.
The New England journal of medicine · 2020 · 384 citations · Europe PMC · via luspatercept
New publication2019-01-07
Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with β-thalassemia.
Blood · 2019 · 80 citations · Europe PMC · via luspatercept
New publication2019-01-02
Luspatercept for the treatment of anemia in myelodysplastic syndromes and primary myelofibrosis.
Blood · 2019 · 76 citations · Europe PMC · via luspatercept

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.