Table 2.
Clinical trials of various diseases by targeting protein lipidation
| Lipidation | Drug | Mechanism | Disease or patients | Treatment | Phase | NCT number |
|---|---|---|---|---|---|---|
| N-myristoylation | PCLX-001 | Pan-NMT inhibitor | Relapsed/refractory B-cell non-Hodgkin lymphoma and advanced solid malignancies | Monotherapy | I | NCT04836195 |
| Asciminib (ABL001) | Target the myristoyl pocket of the BCR-ABL1 tyrosine kinase | Ph+ ALL or CML |
Asciminib in combination with Dasatinib, Prednisone, and Blinatumomab |
I | NCT03595917 | |
| CML |
Monotherapy of imatinib or combination with asciminib; combination of asciminib with TKI |
II | NCT04216563 | |||
| CML | Continued treatment of asciminib | IV | NCT04877522 | |||
| Newly diagnosed CML-CP | Monotherapy or combination with one TKI | II | NCT05143840 | |||
| Newly diagnosed, previously untreated Ph+ CML-CP | Monotherapy of asciminib or nilotinib; or one selected TKI | III | ||||
| CML-CP previously treated with one prior ATP-binding site TKI | Monotherapy | II | NCT05384587 | |||
| Relapsed CML previously attempted to discontinue imatinib | Asciminib combination with imatinib | II/ III | ||||
| CML-CP previously treated with two or more TKIs |
Monotherapy of asciminib; or best available treatment; or bosutinib |
II/III | ||||
|
CML-CP without T315I mutation previously treated with two prior TKIs; CML-CP with T315I mutation with previously treated with at least prior TKIs |
Monotherapy | III | NCT04666259 | |||
| S-prenylation | Pravastatin | Inhibition of FPP and GGPP biosynthesis | HGPS | A combination of zoledronic acid and pravastatin | II | NCT00731016 |
| Zoledronic acid | Inhibition of the FPPS | Progeria; HGPS | A combination of pravastatin and lonafarnib and zoledronic acid | II | ||
| Lonafarnib | FTase inhibitor | HDV infection | Monotherapy | II 11 | NCT01495585 | |
| HDV infection | Lonafarnib in combination with ritonavir | II/III | ||||
| HDV infection | Lonafarnib With or Without Ritonavir | II | ||||
| HDV infection | A combination of Lonafarnib, ritonavir and peginterferon lambda-1a | II | ||||
| BMS-214662 | FTase inhibitor | acute leukaemia, MDS, or CML | Monotherapy | I | NCT00006213 | |
| Solid tumours | Monotherapy | I | ||||
| Advanced solid tumours |
Monotherapy; BMS-214662 in combination with trastuzumab; BMS-214662 in combination with paclitaxel |
I | ||||
| S-prenylation | Lonafarnib | FTase inhibitor | HGPS | monotherapy | II | NCT00425607 |
| Progeria | Lonafarnib in combination with and everolimus | I/II | NCT02579044 | |||
| MDS or CML | Monotherapy | III | NCT00109538 | |||
| Chronic or accelerated phase CML |
Monotherapy; Lonafarnib in combination with Gleevec |
I/II | ||||
| Metastatic breast cancer | Monotherapy | II | NCT00773474 | |||
| Advanced breast cancer |
Lonafarnib in combination with Herceptin Plus Paclitaxel; anastrozole in combination with lonafarnib or monotherapy of anastrozole |
II | ||||
| Recurrent or progressive brain tumours in children | Monotherapy | I | NCT00015899 | |||
| HNSCC | Monotherapy | I/II | ||||
| Advanced or recurrent HNSCC | Lonafarnib in combination with Fenretinide | I | NCT00102635 | |||
| Advanced ovarian carcinoma | Monotherapy | II | NCT00281515 | |||
| Glioblastoma multiforme | Lonafarnib in combination with temozolomide | I | NCT00102648 | |||
| Recurrent glioblastoma multiforme | Lonafarnib in combination with temozolomide | II | NCT00038493 | |||
| Recurrent primary supratentorial gliomas | A combination of lonafarnib and temozolomide | I | NCT00083096 | |||
| Grade 3 & 4 malignant gliomas | Lonafarnib in combination with Temodar | I | NCT00612651 | |||
| Metastatic colorectal cancer | Monotherapy or conventional surgery | I | NCT00005030 | |||
| Stage 3b or 4 NSCLC | Lonafarnib in combination with, paclitaxel and carboplatin | III | NCT00050336 | |||
| Advanced cancer of the urinary tract | Lonafarnib in combination with gemcitabine | II | NCT00006351 | |||
| Advanced malignancies |
Lonafarnib in combination with docetaxel; Lonafarnib in combination with fluorouracil, and leucovorin |
I | ||||
| Tipifarnib | FTase inhibitor | Leukaemia | Monotherapy | I/II | ||
| AML |
Monotherapy; Tipifarnib in combination with chemotherapy; |
I/II/III | ||||
| Advanced haematologic cancer | Monotherapy | I | NCT00005967 | |||
| AML | Tipifarnib in combination with Etoposide | I/II | ||||
| CML-CP | Tipifarnib in combination with Imatinib mesylate | I | NCT00040105 | |||
| Myeloproliferative disorders | Monotherapy | I/II | ||||
| Multiple myeloma | Monotherapy or Tipifarnib in combination with Bortezomib or PS-341 | I/II |
Ph + Philadelphia chromosome positive, ALL acute lymphoblastic leukaemia, CML-CP chronic myelogenous leukaemia in chronic phase, TKI tyrosine kinase inhibitor, HGPS Hutchinson-Gilford progeria syndrome, MDS myelodysplastic syndrome, HNSCC head and neck squamous cell carcinomas, NSCLC non-small cell lung cancer, HDV hepatitis delta virus