ArticleInvestigational new drugs2013
A phase I trial of KX2-391, a novel non-ATP competitive substrate-pocket- directed SRC inhibitor, in patients with advanced malignancies.
Article in Investigational new drugs, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 38 citations in OpenAlex.
- A phase 2 study of KX2-391, an oral inhibitor of Src kinase and tubulin polymerization, in men with bone-metastatic castration-resistant prostate cancer.Cancer chemotherapy and pharmacology · 2013Trial
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- Src and Abl as Therapeutic Targets in Lung Cancer: Opportunities for Drug Repurposing.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Focal adhesion in the tumour metastasis: from molecular mechanisms to therapeutic targets.Biomarker research · 2025Review
- Role of c-Src in Carcinogenesis and Drug Resistance.Cancers · 2023Review
- A phase Ib dose escalation study of oral monotherapy with KX2-391 in elderly patients with acute myeloid leukemia.Investigational new drugs · 2022Article
- Molecular Mechanisms of Cutaneous Squamous Cell Carcinoma.International journal of molecular sciences · 2022Review
- Topical tirbanibulin eradication of periungual squamous cell carcinoma.JAAD case reports · 2021Article
- Targeting p130Cas- and microtubule-dependent MYC regulation sensitizes pancreatic cancer to ERK MAPK inhibition.Cell reports · 2021Article
- Tirbanibulin: First Approval.Drugs · 2021Review
- Tirbanibulin Attenuates Pulmonary Fibrosis by Modulating Src/STAT3 Signaling.Frontiers in pharmacology · 2021Article
- Review
- Reversible binding of the anticancer drug KXO1 (tirbanibulin) to the colchicine-binding site of β-tubulin explains KXO1's low clinical toxicity.The Journal of biological chemistry · 2019Article
- A phase I study of gemcitabine + dasatinib (gd) or gemcitabine + dasatinib + cetuximab (GDC) in refractory solid tumors.Cancer chemotherapy and pharmacology · 2019Article
- Tyrosyl phosphorylation of KRAS stalls GTPase cycle via alteration of switch I and II conformation.Nature communications · 2019Article
- Targeting Upstream Kinases of STAT3 in Human Medulloblastoma Cells.Current cancer drug targets · 2019Article
- Targeting Src attenuates peritoneal fibrosis and inhibits the epithelial to mesenchymal transition.Oncotarget · 2017Article
- High-Throughput Screening of Myxoid Liposarcoma Cell Lines: Survivin Is Essential for Tumor Growth.Translational oncology · 2017Article
- Antitumor Effect of KX-01 through Inhibiting Src Family Kinases and Mitosis.Cancer research and treatment · 2017Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundSrc kinase is central to tumor cell proliferation, apoptosis, and metastasis. KX2-391 is a synthetic, orally bioavailable small molecule inhibitor of Src tyrosine kinase (TK) signaling and tubulin polymerization. This compound is distinct from other Src kinase inhibitors by targeting the peptide substrate rather than the ATP binding site; the binding site on hetero-dimeric tubulin is novel and distinct from the taxanes and other known tubulin inhibitors.
methodsThis multicenter Phase I trial utilized a 4 + 2 study design to determine the maximum tolerated dose (MTD), safety, and pharmacokinetics (PK) of KX2-391 in patients with refractory solid tumors.
resultsForty-four (44) patients (18 M, 26 F; median age, 59) were enrolled in 9 dose cohorts. Dose-limiting toxicities, all reversible within 7 days, occurred in 7 patients and consisted of elevated AST (n = 4), ALT (n = 2), neutropenia (n = 1), thrombocytopenia (n = 1), failure to thrive (n = 1) and anorexia (n = 1). The MTD is 40 mg BID continuously. Eleven patients had stable disease for ≥ 4 months, including patients with ovarian, carcinoid, papillary thyroid, prostate, pancreas and head and neck cancer. Patients with prostate and pancreatic cancer also had significant biomarker decreases (PSA, 205 ng/mL to 39 ng/mL; CA19-9, 38,838 U/mL to 267 U/mL). The ovarian cancer patient has had stable disease > 12 months. KX2-391 was orally available, rapidly absorbed, and exposure was proportional to dose across the range investigated.
conclusionsKX2-391 has a favorable pharmacokinetic profile, is well tolerated, demonstrates preliminary evidence of biologic activity, and warrants further evaluation in Phase II trials.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.