Temsirolimus

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Cat Number

API0232128

CAS Number

162635-04-3

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CAS Number

162635-04-3

EINECS

686-177-0

Storage

Store at 2-8°C

Synonyms

Torisel; 624KN6GM2T; DTXCID0020945; Rapamycin 42-(2,2-bis(hydroxymethyl)propionate)

Molecular Formula

C56H87NO16

Molecular Weight

1030.3

Smiles

C[C@@H]1CC[C@H]2C[C@@H](/C(=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]([C@@H](/C(=C/[C@H](C(=O)C[C@H](OC(=O)[C@@H]3CCCCN3C(=O)C(=O)[C@@]1(O2)O)[C@H](C)C[C@@H]4CC[C@H]([C@@H](C4)OC)OC(=O)C(C)(CO)CO)C)/C)O)OC)C)C)/C)OC

Melting Point

99-101°C

Boiling Point

1048.4°C at 760 mmHg (Predicted)

Relative Density

1.2

General Description

Temsirolimus is a synthetic ester derivative of sirolimus (rapamycin), specifically the 42-[2,2-bis(hydroxymethyl)propionate] analog. This modification improves aqueous solubility and allows intravenous administration. The molecule retains the macrocyclic lactone structure of sirolimus but with a substituted triene ring system, and serves as a prodrug that is converted to sirolimus in vivo.

Mechanism of Action

Temsirolimus binds to the immunophilin FKBP-12, and the complex inhibits the mammalian target of rapamycin (mTOR) kinase activity. This prevents phosphorylation of downstream effectors such as p70S6 kinase and 4E-BP1, leading to cell cycle arrest in the G1 phase. The drug selectively blocks mTOR complex 1 (mTORC1) with minimal direct activity against mTORC2.

Application

Temsirolimus is indicated for the treatment of advanced renal cell carcinoma (RCC), particularly in patients with poor prognostic features. It exhibits antiproliferative and antiangiogenic activity by suppressing hypoxia-inducible factor (HIF) translation. The prodrug nature allows more predictable pharmacokinetics than sirolimus, with the parent compound serving as a reservoir for active drug release.

The phase I/II trial of temsirolimus (25 mg weekly) plus lenalidomide (20 mg on days 1‑21 of a 28‑day cycle) in relapsed/refractory lymphoma established the recommended phase II dose. Among heavily pretreated patients (median 4 prior therapies), the objective response rate was 26% in diffuse large B‑cell lymphoma (13% complete) and 64% in an exploratory cohort (mostly classical Hodgkin lymphoma). In cHL, many after brentuximab vedotin and autologous stem cell transplant, the ORR reached 80% (35% complete). Grade ≥3 hematologic toxicities were common, but the combination was feasible with encouraging activity, particularly in relapsed/refractory cHL.

Fig. 1 Waterfall plot for best response for evaluable patients in the phase II study by histology (n=74). (Major A, et al., 2022)

References

Major A, et al. Phase I/II clinical trial of temsirolimus and lenalidomide in patients with relapsed and refractory lymphomas. Haematologica. 2022;107(7):1608-1618.

This phase I trial (48 heavily pretreated patients, median 4 prior therapies) evaluated bevacizumab 10 mg/kg biweekly plus temsirolimus 20 mg weekly (MTD). Dose‑limiting toxicities included enteritis, fatigue, bowel obstruction, perforation, and elevated liver enzymes. Grade ≥3 adverse events occurred in 31.3%. Objective response rate was 7.3%, with stable disease ≥6 months in 19.5% (clinical benefit rate 26.8%). In the ovarian expansion cohort (16.7% ORR, 33.3% CBR), modest activity was observed. The combination showed acceptable safety but limited efficacy; exploratory molecular and imaging findings may inform future biomarker studies.

Fig. 2 Results of DCE-MRI for each patient subgroup. (Piha-Paul SA, et al., 2026)

References

Piha-Paul SA, et al. Phase I study of bevacizumab and temsirolimus combination therapy in advanced malignancies: safety, efficacy, and ovarian cancer expansion. Oncologist. 2026;31(3):oyaf413.

Does Temsirolimus require strict cold chain storage as a mTOR inhibitor?

Yes, it must be stored at 2-8°C. The compound is thermally labile; at room temperature, degradation via isomerization and ester hydrolysis occurs rapidly.

Is Temsirolimus sensitive to light and moisture?

Yes, it is both photosensitive and hygroscopic. Store in original, tightly sealed, light-resistant containers with desiccant under refrigeration.

What is the stability of Temsirolimus after reconstitution for intravenous infusion?

Reconstituted solutions (in D5W or saline) must be used within 24 hours under refrigeration. Avoid freeze-thaw cycles.

How is the impurity sirolimus (de-esterified temsirolimus) monitored?

This primary hydrolysis product is specifically quantified using a stability-indicating HPLC method, ensuring it remains within ICH qualification thresholds.