Dolastatin 10
Also known as: Dol-10, Dola-10, Dolastatin-10, NSC-376128
Source Dolastatin 10 at Peptiology
Save 10% with code PEPTI-BOSSRABBIT-10
Affiliate link: we earn a commission on purchases made through this link, at no extra cost to you.
Tapping Shop Now & Save 10% copies your 10% off code PEPTI-BOSSRABBIT-10 to your clipboard. Paste it at the Peptiology checkout to claim the discount.
Summary
Dolastatin 10 is a marine‑derived pentapeptide that potently inhibits tubulin polymerisation, leading to cell‑cycle arrest and apoptosis. Although the naked compound has not been approved because its toxicity could not be separated from efficacy, its highly cytotoxic core has been repurposed as the payload for several antibody‑drug conjugates (ADCs) that are approved for certain lymphomas. Early laboratory work also identified nanomolar antiplasmodial activity.
Mechanism of Action
Dolastatin 10 binds to the vinca‑binding site on β‑tubulin, preventing the addition of tubulin dimers to growing microtubules. This blocks microtubule assembly, halting mitotic spindle formation and arresting cells in the G2/M phase. The resulting mitotic failure triggers apoptotic pathways in rapidly dividing cells, accounting for its nanomolar cytotoxicity against many tumour lines.
What the Research Shows
Reviews of marine natural‑product discovery highlight Dolastatin 10 as a key antimitotic peptide identified from the mollusk Dolabella auricularia. Structure‑activity studies showed that modifications at the C‑ and N‑termini retain potency, leading to synthetic analogues such as monomethyl auristatin E (MMAE) and F (MMAF). Early clinical trials of the parent peptide and its C‑terminal analogue auristatin PE showed limited success because systemic toxicity overlapped with efficacy. The extreme potency of the scaffold spurred its incorporation into ADCs, where conjugation to tumour‑specific antibodies reduces off‑target exposure. Four ADCs carrying MMAE or MMAF have received regulatory approval, and more than 36 ADCs using related pentapeptide payloads are in pre‑clinical or clinical evaluation. In addition, in vitro screens identified Dolastatin 10 as a nanomolar inhibitor of Plasmodium parasites, classifying it as a cytoskeletal disruptor with antiplasmodial potential.
Reported Benefits
Dolastatin 10 exhibits nanomolar cytotoxicity against a broad range of cancer cell lines, including leukemia, small‑cell lung carcinoma, and prostate cancer, making it a powerful tool for targeted drug design. Its incorporation into ADCs has produced approved therapies (e.g., Adcetris®) that deliver the payload selectively to CD30‑positive lymphomas, improving therapeutic indices. Preliminary antiplasmodial screens also suggest potential utility against malaria parasites at very low concentrations.
Limitations of the Evidence
The free peptide has not progressed to market because clinical studies could not uncouple its potent anti‑tumour activity from severe systemic toxicity. Evidence for efficacy in humans is therefore limited to its role as an ADC payload, not as a standalone drug. Antiplasmodial activity has only been demonstrated in vitro, with no in‑vivo data. Much of the mechanistic and SAR information derives from pre‑clinical models, and long‑term safety of the payload within ADCs remains under investigation.
Safety Considerations
Dolastatin 10’s mechanism of tubulin inhibition leads to high cytotoxicity that can affect normal dividing cells, resulting in dose‑limiting toxicities such as neutropenia, neuropathy, and gastrointestinal effects in early trials. While conjugation to antibodies mitigates systemic exposure, ADCs that incorporate MMAE or MMAF still report class‑related adverse events typical of tubulin inhibitors. No formal safety profile exists for the unconjugated peptide, and caution is advised when interpreting pre‑clinical toxicity data.
How It Is Administered
Research‑grade Dolastatin 10 is administered intravenously in laboratory settings. In clinical contexts the molecule is not used alone but is chemically linked to monoclonal antibodies, forming ADCs that are also given by intravenous infusion. Formulations are typically sterile solutions suitable for infusion over a defined period.
Routes of Administration
Goals & Uses
- Anticancer activityOncologyModerate
- Cancer chemotherapyOncologyModerate
- Tubulin inhibition researchBasic ResearchHigh
- ADC payload scaffoldDrug DevelopmentHigh
Contraindications
- Severe hepatic impairmentOrganModerateLiver function concerns
- PregnancyPopulationHighPotential fetal risk or insufficient safety data
- Severe bone marrow suppressionHematologicHigh
Adverse Effects
- Peripheral neuropathyNeurologicalCommon
- Myelosuppression / neutropeniaHematologicCommon
- AlopeciaDermatologicCommonHair loss
- ConstipationGastrointestinalUncommonReduced bowel frequency or difficulty passing stool
- Nausea and vomitingGastrointestinalCommon
- NeutropeniaHematologicCommonLow neutrophil count
- FatigueGeneralCommonLow energy or tiredness
Drug Interactions
- Vinca alkaloidsModerate
- CYP3A4 inhibitors (e.g., ketoconazole)Moderate
- Other myelosuppressive agentsHigh
Population Constraints
- PregnancyReproductive SafetyAbsolute
- Pediatric patientsAgeRelative
- Severely immunocompromised patientsImmunologicalRelative
- Pregnant womenReproductiveAbsolute
- Patients with pre-existing neuropathyNeurologicRelative
Regulatory Status
- European UnionInvestigationalSame as US.
- United StatesInvestigationalPhase I/II trials discontinued; not approved.
- United KingdomUnapprovedNo MHRA approval; research compound only
No regulatory approval; clinical development discontinued due to severe myelosuppression and neurotoxicity.
Evidence & Sources
- Journal ArticleModerateStuart KA, et al.2020-01-01T00:00:00.000000Z
- Journal ArticleModerate2011-01-01T00:00:00.000000Z
- Journal ArticleModerateKingston DG2009-01-01T00:00:00.000000Z
- Journal ArticleModerateSingh SB2022-01-01T00:00:00.000000Z
- Journal ArticleModerateAlvarez-Sánchez ME, et al.2024-01-01T00:00:00.000000Z
- Journal ArticleModerateGao G, et al.2021-01-01T00:00:00.000000Z
Frequently Asked Questions
Why was Dolastatin 10 never approved as a stand‑alone cancer drug?
Early human trials showed that the peptide’s potent anti‑tumour activity was accompanied by severe systemic toxicity, making it impossible to achieve a therapeutic window. Consequently, development shifted to using its cytotoxic core as a payload within antibody‑drug conjugates, which can target delivery to tumour cells.
What makes Dolastatin 10 useful for antibody‑drug conjugates?
Its nanomolar potency against microtubules means that only a few molecules are needed to kill a cancer cell, allowing a low drug‑to‑antibody ratio. When linked to an antibody that recognises a tumour‑specific antigen, the payload is delivered directly to the malignant cells, reducing exposure of healthy tissue.
Has Dolastatin 10 shown any activity against malaria?
In vitro screening of marine cyanobacterial metabolites identified Dolastatin 10 as one of two compounds with sub‑nanomolar inhibition of Plasmodium parasites. The activity is attributed to its ability to disrupt the parasite’s cytoskeleton, but no animal or clinical data have been reported.
Are there any approved drugs that contain Dolastatin 10‑derived payloads?
Yes. Four ADCs – brentuximab vedotin (Adcetris®), enfortumab vedotin (Padcev®), polatuzumab vedotin (Polivy®), and belantamab mafodotin (Blenrep®) – use monomethyl auristatin E or F, synthetic analogues of Dolastatin 10, as their cytotoxic component.
What are the main safety concerns when using Dolastatin 10‑based ADCs?
Even when targeted, the tubulin‑inhibiting payload can cause class‑related toxicities such as peripheral neuropathy, neutropenia, and gastrointestinal effects. Monitoring for these adverse events is standard in clinical trials and post‑marketing surveillance of ADCs.
What is Dolastatin 10?
Dolastatin 10 is a marine‑derived pentapeptide that potently inhibits tubulin polymerisation, leading to cell‑cycle arrest and apoptosis. Although the naked compound has not been approved because its toxicity could not be separated from efficacy, its highly cytotoxic core has been repurposed as the payload for several antibody‑drug conjugates (ADCs) that are approved for certain lymphomas. Early laboratory work also identified nanomolar antiplasmodial activity.
What is Dolastatin 10 used for?
Dolastatin 10 is educationally associated with: Anticancer activity, Cancer chemotherapy, Tubulin inhibition research, ADC payload scaffold. Educational only — not medical advice.
How is Dolastatin 10 administered?
Recorded routes of administration: Intravenous.
What are the potential side effects of Dolastatin 10?
Reported adverse effects include: Peripheral neuropathy, Myelosuppression / neutropenia, Alopecia, Constipation, Nausea and vomiting, Neutropenia, Fatigue. This list is not exhaustive — consult a qualified clinician.
Who should avoid Dolastatin 10?
Recorded contraindications: Severe hepatic impairment, Pregnancy, Severe bone marrow suppression. Consult a qualified clinician before use.