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DRUG CLASS:

DNA topoisomerase inhibitor

2d
Transurethral resection of bladder tumor with Bacille Calmette-Guerin intravesical instillation for HRNMIBC and factors influencing recurrence. (PubMed, Am J Transl Res)
The combination of TURBT with pirarubicin and BCG intravesical instillation significantly lowers the recurrence rate in HRNMIBC patients and enhances both quality of life and immune function recovery. Independent factors affecting HRNMIBC recurrence include tumor number, stage, grade, and primary tumor status.
Journal
|
CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
|
Pinorubin (pirarubicin)
23d
Flavored, Oral Irinotecan VAL-413 (Orotecan®) Given With Temozolomide for Treatment of Recurrent Pediatric Solid Tumors (clinicaltrials.gov)
P1, N=20, Recruiting, Valent Technologies, LLC | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025
Trial completion date • Trial primary completion date
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temozolomide
28d
Study of Liposomal Annamycin in Combination with Cytarabine for the Treatment of Subjects with Acute Myeloid Leukemia (AML) (clinicaltrials.gov)
P1/2, N=63, Active, not recruiting, Moleculin Biotech, Inc. | Recruiting --> Active, not recruiting
Enrollment closed • Combination therapy
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liposomal annamycin (L-ANN)
28d
Trial termination
1m
New P3 trial
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topotecan • pegylated irinotecan (SSS22)
2ms
Study of Liposomal Annamycin for the Treatment of Subjects with Soft-Tissue Sarcomas (STS) with Pulmonary Metastases (clinicaltrials.gov)
P1/2, N=36, Completed, Moleculin Biotech, Inc. | Active, not recruiting --> Completed | Phase classification: P1b/2 --> P1/2 | Trial completion date: May 2024 --> Aug 2024
Trial completion • Phase classification • Trial completion date
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liposomal annamycin (L-ANN)
3ms
Comparison of neoadjuvant chemotherapy response and prognosis among pegylated liposomal doxorubicin, epirubicin and pirarubicin in HR ⩽ 10%/HER2-negative breast cancer: an exploratory real-world multicentre cohort study. (PubMed, Ther Adv Med Oncol)
For patients with pCR, the differences in EFS (log-rank p = 0.47) and OS (log-rank p = 0.38) were not statistically significant among the three groups, and the EFS (log-rank p = 0.59) and OS (log-rank p = 0.14) of non-pCR patients in the PLD group were similar to those in the epirubicin and pirarubicin groups. PLD had a similar therapeutic response and prognosis compared to epirubicin or pirarubicin in NAC for patients with HR ⩽ 10%/HER2 negative breast cancer, which means that PLD represents a potential NAC option.
Journal • Real-world evidence • Real-world
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 negative
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pegylated liposomal doxorubicin • epirubicin • Pinorubin (pirarubicin)
3ms
New P2 trial • Surgery
|
temozolomide • pegylated irinotecan (SSS22)
3ms
New P2 trial
|
pegylated irinotecan (SSS22)
3ms
Pirarubicin combined with TLR3 or TLR4 agonists enhances anti-tumor efficiency. (PubMed, Int Immunopharmacol)
Our results provide new ideas for the combination strategy of THP with TLR agonists which improves prognosis of breast cancer.
Journal • IO biomarker
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TLR4 (Toll Like Receptor 4) • TLR3 (Toll Like Receptor 3)
|
Pinorubin (pirarubicin)
4ms
New P3 trial
|
topotecan • pegylated irinotecan (SSS22)
4ms
DB-1314, a novel DLL3-targeting ADC with DNA topoisomerase I inhibitor, exhibits promising safety profile and therapeutic efficacy in preclinical small cell lung cancer models. (PubMed, J Transl Med)
These results suggest that DB-1314 may be a candidate ADC targeting DLL3 for the treatment of DLL3-positive SCLC, supporting further evaluation in the clinical setting.
Preclinical • Journal
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DLL3 (Delta Like Canonical Notch Ligand 3)
|
Rova-T (rovalpituzumab tesirine)
5ms
Does Topical Otic Drop Use at Time of Tympanostomy Tube Surgery Improve Outcomes When no Middle Ear Effusion is Present (clinicaltrials.gov)
P4, N=125, Recruiting, Boston Children's Hospital | Trial completion date: Sep 2025 --> Sep 2026
Trial completion date • Surgery
7ms
Berberine increases the killing effect of pirarubicin on HCC cells by inhibiting ATG4B-autophagy pathway. (PubMed, Exp Cell Res)
Tumor-bearing experiments in nude mice showed that the combination treatment with BBR and THP significantly suppressed the growth of HCC xenografts. These results reveal that BBR is able to strengthen the killing effect of THP on HCC cells by repressing the ATG4B-autophagy pathway, which may provide novel insights into the improvement of chemotherapeutic efficacy of THP, and may be conducive to the further clinical application of THP in HCC treatment.
Journal
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HIF1A (Hypoxia inducible factor 1, alpha subunit) • ATG4B (Autophagy Related 4B Cysteine Peptidase)
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HIF1A expression
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Pinorubin (pirarubicin)
8ms
DB-1310, an ADC comprised of a novel anti-HER3 antibody conjugated to a DNA topoisomerase I inhibitor, is highly effective for the treatment of HER3-positive solid tumors. (PubMed, J Transl Med)
These finding demonstrated that DB-1310 exerted potent antitumor activities against HER3 + tumors in in vitro and in vivo models, and showed acceptable safety profiles in nonclinical species. Therefore, DB-1310 may be effective for the clinical treatment of HER3 + solid tumors.
Journal
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HER-2 (Human epidermal growth factor receptor 2)
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ERBB3 overexpression • ERBB3 positive
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Tagrisso (osimertinib) • patritumab deruxtecan (U3-1402) • DB-1310
9ms
Food therapy of scutellarein ameliorates pirarubicin‑induced cardiotoxicity in rats by inhibiting apoptosis and ferroptosis through regulation of NOX2‑induced oxidative stress. (PubMed, Mol Med Rep)
However, cell treatment with the ferroptosis inhibitor, ferrostatin‑1, or inducer, erastin, could not significantly reduce or promote, respectively, the expression of NOX2. However, GSK significantly affected ferroptosis and GPX4 expression. Overall, the results of the present study indicated that food therapy with Sc ameliorated CTP via inhibition of apoptosis and ferroptosis through regulation of NOX2‑induced oxidative stress, thus suggesting that Sc may be a potential therapeutic drug against CTP.
Preclinical • Journal
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GPX4 (Glutathione Peroxidase 4)
|
GPX4 expression
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erastin • Pinorubin (pirarubicin)
10ms
DNA topoisomerase II inhibition potentiates osimertinib's therapeutic efficacy in EGFR-mutant non-small cell lung cancer models. (PubMed, J Clin Invest)
This study reported that the DNA topoisomerase II (Topo II) inhibitors, doxorubicin and etoposide (VP-16) synergistically decreased cell survival with enhanced induction of DNA damage and apoptosis in osimertinib-resistant cells, suppressed the growth of osimertinib-resistant tumors, and delayed the emergence of osimertinib acquired resistance. Enforced expression of an ectopic TOP2A gene in sensitive EGFRm NSCLC cells conferred resistance to osimertinib, whereas knockdown of TOP2A in osimertinib-resistant cell lines restored their response to undergo osimertinib-induced DNA damage and apoptosis. Together, these results reveal an essential role of Topo IIα inhibition in mediating the therapeutic efficacy of osimertinib against EGFRm NSCLC, providing scientific rationale for targeting Topo II to manage acquired resistance to osimertinib.
Preclinical • Journal
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EGFR (Epidermal growth factor receptor) • TOP2A (DNA topoisomerase 2-alpha) • FBXW7 (F-Box And WD Repeat Domain Containing 7)
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EGFR mutation • TOP2A expression
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Tagrisso (osimertinib) • doxorubicin hydrochloride • etoposide IV
10ms
CircZCCHC2 decreases pirarubicin sensitivity and promotes triple-negative breast cancer development via the miR-1200/TPR axis. (PubMed, iScience)
It is demonstrated that circZCCHC2 plays a crucial role in the malignant progression of TNBC via the miR-1200/TPR axis, thereby activating the RAS-RAF-MEK-ERK pathway. The present results indicate that circZCCHC2 has the potential to serve as a novel prognostic biomarker for TNBC.
Journal
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TPR (Translocated Promoter Region) • MIR1200 (MicroRNA 1200)
|
Pinorubin (pirarubicin)
10ms
Validation of hyperthermia as an enhancer of chemotherapeutic efficacy: insights from a bladder cancer organoid model. (PubMed, Int J Hyperthermia)
The resulting organoids were treated with pirarubicin or gemcitabine at 37 °C or 42 °C. Finally, RNA sequencing revealed the IFN-γ signaling pathway to be associated with hyperthermia. Overall, hyperthermia combined with chemotherapy exerted better therapeutic effects than those of normothermic chemotherapy in grade 1-2 non-muscle-invasive bladder cancer, potentially through activation of the IFN-γ-JAK-STAT pathway.
Journal
|
IFNG (Interferon, gamma)
|
gemcitabine • Pinorubin (pirarubicin)
11ms
Raludotatug Deruxtecan, a CDH6-Targeting Antibody-Drug Conjugate with a DNA Topoisomerase I Inhibitor DXd, is Efficacious in Human Ovarian and Kidney Cancer Models. (PubMed, Mol Cancer Ther)
R-DXd demonstrated potent antitumor activity against CDH6-expressing tumors in mice and an acceptable safety profile in monkeys. These findings indicate the potential of R-DXd as a new treatment option for patients with CDH6-expressing serous-type ovarian cancer and renal cell carcinoma in a clinical setting.
Preclinical • Journal
|
CHEK1 (Checkpoint kinase 1) • CASP3 (Caspase 3) • CDH6 (Cadherin 6)
|
CDH6 expression
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raludotatug deruxtecan (DS-6000)
1year
A Study of Bi-Ligand-Drug Conjugate CBP-1019 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
P1/2, N=260, Recruiting, Coherent Biopharma (Hefei) Co., Ltd. | Active, not recruiting --> Recruiting
Enrollment open
|
FOLR1 ( Folate receptor alpha ) • TRPV6 (Transient Receptor Potential Cation Channel Subfamily V Member 6)
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CBP-1019
1year
Preliminary Results from a Phase 1/2 Study of Liposomal Annamycin (L-ANN) in Combination with Cytarabin for the Treatment of Patients with Acute Myeloid Leukemia (AML) That Is Refractory to or Relapsed (r/r) after Induction Therapy (ASH 2023)
The design of the novel liposomal L-annamycin (L-ANN) was the replacement of a basic amine at the C-3' position with a hydroxy group, which was shown to significantly reduce cardiotoxicity when compared with doxorubicin...All patients will also receive cytarabine 2... Initial data suggested that L-ANN is safe and active in heavily pretreated r/r AML patients with no signs of cardiotoxicity. This study is currently being conducted in Europe across 5 sites in Poland and 3 in Italy. Results from the Phase 2 portion of this study will be presented at the meeting.
Clinical • P1/2 data • Combination therapy
|
ABCB1 (ATP Binding Cassette Subfamily B Member 1)
|
cytarabine • doxorubicin hydrochloride • liposomal annamycin (L-ANN)
1year
Dose-finding Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of SNB-101(SN-38) in Patients With Tumors (clinicaltrials.gov)
P1, N=36, Not yet recruiting, SN BioScience | Trial completion date: Dec 2023 --> Jun 2025 | Trial primary completion date: May 2023 --> Dec 2024
Trial completion date • Trial primary completion date • Metastases
|
SNB-101
1year
Study of Liposomal Annamycin for the Treatment of Subjects With Soft-Tissue Sarcomas (STS) With Pulmonary Metastases (clinicaltrials.gov)
P1b/2, N=36, Active, not recruiting, Moleculin Biotech, Inc. | Recruiting --> Active, not recruiting | N=55 --> 36 | Trial primary completion date: Aug 2023 --> May 2024
Enrollment closed • Enrollment change • Trial primary completion date
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liposomal annamycin (L-ANN)
1year
Astaxanthin protects against pirarubicin-induced H9c2 cardiomyocytes by adjusting microRNA-494-3p-mediated MDM4/p53 signalling pathway. (PubMed, J Pharm Pharmacol)
AST can inhibit H9c2 apoptosis induced by THP and attenuate H9c2 damage by THP, which may be achieved by downregulating miR-494-3p, upregulating MDM4, and inhibiting p53.
Journal
|
MDM4 (The mouse double minute 4) • MIR494 (MicroRNA 494)
|
TP53 expression • miR-494 overexpression
|
Pinorubin (pirarubicin)
1year
LncRNA Miat knockdown protects against pirarubicin-induced cardiotoxicity by targeting miRNA-129-1-3p. (PubMed, Environ Toxicol)
Knockdown of miR-129-1-3p reversed the protective effect of Miat knockdown on HL-1. Miat knockdown can alleviate THP-induced cardiomyocyte injury by regulating miR-129-1-3p.
Journal
|
MIAT (Myocardial Infarction Associated Transcript) • MIR129 (MicroRNA 129) • MIR129-1 (MicroRNA 129-1)
|
Pinorubin (pirarubicin)
1year
Mechanisms of Secondary Leukemia Development Caused by Treatment with DNA Topoisomerase Inhibitors. (PubMed, Biochemistry (Mosc))
Recurrent chromosomal translocations in the therapy-related leukemia differ from chromosomal rearrangements associated with other neoplasias. Here, we reviewed the factors that drive chromosomal translocations induced by cancer treatment with DNA topoisomerase II inhibitors, such as mobility of ends of double-strand DNA breaks formed before the translocation and gain of function of fusion proteins generated as a result of translocation.
Review • Journal
|
KMT2A (Lysine Methyltransferase 2A)
over1year
Discovery of VIP236, an αvβ3-Targeted Small-Molecule-Drug Conjugate with Neutrophil Elastase-Mediated Activation of 7-Ethyl Camptothecin Payload for Treatment of Solid Tumors. (PubMed, Cancers (Basel))
Treatment with VIP236 resulted in long-lasting tumor regression in subcutaneous patient-derived xenograft (PDX) models from patients with non-small-cell lung, colon, and renal cancer as well as in two orthotopic metastatic triple-negative breast cancer PDX models. In these models, a significant reduction of brain and lung metastases also was observed.
Journal
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VIP236
over1year
Full-profile pharmacokinetics, anticancer activity and toxicity of an extended release trivalent PEGylated irinotecan prodrug. (PubMed, Acta Pharm Sin B)
In summary, PEG-[Irinotecan] displays superior pharmacokinetic characteristics and antitumor activity with lower toxicity than irinotecan. This supports the view that PEG-[Irinotecan] is a superior anticancer drug to irinotecan and it has entered the phase II trial stage.
PK/PD data • Journal
|
irinotecan • Onzeald (etirinotecan pegol) • pegylated irinotecan (SSS22)
over1year
Analysis of risk factors for recurrence after transurethral resection of bladder tumor in patients with non-muscle invasive bladder cancer: 2-year follow-up outcomes. (PubMed, Oncology)
Our study highlights the importance of postoperative surveillance and individualized treatment for patients with NMIBC. Our findings show that high pathology grading, pirarubicin treatment, and BCG treatment are independent risk factors for recurrence after TURBT in patients with NMIBC. However, caution is warranted when interpreting our findings due to the small sample size and the need for further research to confirm the negative impact of Mitomycin and BCG on recurrence rates.
Journal
|
gemcitabine • mitomycin • Pinorubin (pirarubicin)
over1year
LncRNA Miat knockdown enhances pirarubicin-mediated anticancer sensitivity in breast cancer cells. (PubMed, Environ Toxicol)
This may be related to the reduction of calcium ions in 4T1. In conclusion, Miat knockdown enhanced the sensitivity of THP to 4T1 by inhibiting calcium channels.
Journal
|
MIAT (Myocardial Infarction Associated Transcript)
|
Pinorubin (pirarubicin)
over1year
Bispecific-XDC: Novel First-in-Class Cancer Therapies From Concept to Clinical (ADC-USA 2023)
Describing CBP-1008: a FR/ TRPV6 targeted drug conjugate in Phase II pivotal studies of advanced ovarian cancer treatment; Exploring CBP-1018: a FR/ PSMA targeted drug conjugate in Phase Ib for prostate cancer therapy; Highlighting CBP-1019: TOP1i payload drug conjugate for unmet medical needs
Clinical
|
TRPV6 (Transient Receptor Potential Cation Channel Subfamily V Member 6)
|
CBP-1008 • CBP-1018 • CBP-1019
over1year
The application of gemcitabine and pirarubicin in patients with non-muscle invasive bladder cancer. (PubMed, J Cancer Res Clin Oncol)
Gemcitabine and pirarubicin are both effective in treating patients with non-muscle invasive bladder cancer, with gemcitabine having a lower incidence of adverse reactions, a higher safety rating, a lower recurrence rate and an improved survival outcome.
Journal
|
gemcitabine • Pinorubin (pirarubicin)
over1year
Predictive profiling of gram-negative antibiotics in CagA oncoprotein inactivation: a molecular dynamics simulation approach. (PubMed, SAR QSAR Environ Res)
The residues ASP96, GLN100, PRO184, and THR185 of compound cefpiramide, doxycycline, delafloxacin, metacycline, oxytetracycline, and ertapenem were involved in the binding with CagA protein. These residues are crucial for the CagA that aids in entry or pathogenesis of the bacterium. The screened FDA-approved antibiotics have a potential druggability to inhibit CagA and reduce the progression of H. pylori borne diseases.
Journal • Gram negative
over1year
CircEGFR reduces the sensitivity of pirarubicin and regulates the malignant progression of triple-negative breast cancer via the miR-1299/EGFR axis. (PubMed, Int J Biol Macromol)
Silencing circEGFR inhibited the malignant progression of the tumor. These results revealed circEGFR is a promising biomarker for TNBC diagnosis, therapeutic and prognosis.
Journal
|
MIR1299 (MicroRNA 1299)
|
Pinorubin (pirarubicin)
over1year
Targeted hollow pollen silica nanoparticles for enhanced intravesical therapy of bladder cancer. (PubMed, Biomater Sci)
In the present study, hollow pollen silica (HPS) nanoparticles (NPs) were prepared and modified with CPBA to form CHPS NPs, which could be further loaded with pirarubicin (THP) to form THP@CHPS NPs...Moreover, THP@CHPS NPs exhibited excellent biocompatibility. THP@CHPS NPs hold great potential for intravesical treatment of bladder cancer.
Journal
|
Pinorubin (pirarubicin)
over1year
Combined use of a 980‑nm diode laser and preoperative intravesical instillation of pirarubicin for the prevention of short‑term recurrence of non‑muscle invasive bladder cancer: A pilot study. (PubMed, Oncol Lett)
Preoperative intravesical instillation of THP is conducive to identifying suspicious lesions. The combination of a 980-nm laser with preoperative THP intravesical instillation can significantly prolong RFS time.
Journal
|
Pinorubin (pirarubicin)
over1year
Study of Liposomal Annamycin for the Treatment of Subjects With Soft-Tissue Sarcomas (STS) With Pulmonary Metastases (clinicaltrials.gov)
P1b/2, N=55, Recruiting, Moleculin Biotech, Inc. | Trial primary completion date: May 2023 --> Aug 2023
Trial primary completion date
|
liposomal annamycin (L-ANN)
over1year
Modified BFM-95 Regimen as First-Line Chemotherapy in Adults With T- Lymphoblastic Lymphoma (clinicaltrials.gov)
P2, N=50, Recruiting, Sun Yat-sen University | Unknown status --> Recruiting | Trial completion date: Mar 2021 --> Mar 2025 | Trial primary completion date: Mar 2021 --> Mar 2025
Enrollment open • Trial completion date • Trial primary completion date
|
cytarabine • cyclophosphamide • vincristine • prednisone • dexamethasone • Oncaspar liquid (pegaspargase) • mercaptopurine • Pinorubin (pirarubicin)