Agents in development for MDS in clinical trials that are actively recruiting patients
| Agent (synonyms) . | Putative mechanism . |
|---|---|
| Kinase inhibitors | |
| INCB047986 | Janus-associated kinase (JAK) inhibitor |
| KB004 | Antibody against ephrin A3 (EphA3) receptor tyrosine kinase |
| LGH447 | Pim kinase inhibitor |
| MEK 162 | Inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2) |
| Midostaurin (PKC412) | Protein kinase C (PKC) inhibitor |
| PD-616 (12-O-tetradecanoylphorbol-13-acetate) | Protein kinase C (PKC) inhibitor |
| Quizartinib (AC220) | Fms-like tyrosine kinase 3 (FLT3) inhibitor |
| Rigosertib (SyB C-1101, SyB L-1101, ON 01910.Na) | Phosphoinositide-3 (PI3) kinase inhibitor, Polo-like kinase pathway inhibitor |
| Ruxolitinib (INCB18424) | Janus-associated kinase (JAK) inhibitor |
| Sorafenib | Inhibition of Raf, vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), Fms-like tyrosine kinase 3 (FLT3) and other kinases |
| Volasertib (BI 6727) | Polo-like kinase 1 (PLK1) inhibitor |
| ziv-Aflibercept | Vascular endothelial growth factor (VEGF) inhibitor |
| Deacetylase inhibitors and DNA methyltransferase inhibitors | |
| Oral azacitidine (CC-486) | DNA methyltransferase inhibitor |
| Oral decitabine and E7727 (ASTX727) | DNA methyltransferase inhibitor combined with cytidine deaminase inhibitor |
| SGI-110 | Nucleoside analog with DNA methyltransferase inhibitory activity |
| Mocetinostat (MGCD0103) | Deacetylase inhibitor |
| Panobinostat (LBH-589) | Deacetylase inhibitor |
| Pracinostat (SB939) | Deacetylase inhibitor |
| Vorinostat (suberanilohydroxamic acid, SAHA) | Deacetylase inhibitor |
| Altered cell metabolism | |
| AG-120, AG-221 | Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) inhibitors |
| Coenzyme Q10 and l-carnitine | Alteration of intracellular metabolism and electron transport chain |
| CPI613 | Inhibition of pyruvate dehydrogenase and ketoglutarate dehydrogenase |
| INCB024360 | Indoleamine 2,3-dioxygenase (IDO1) inhibitor |
| Cytotoxic agents/cell cycle inhibitors | |
| Cladribine (2-CDA) | Nucleoside analog |
| Clofarabine | Nucleoside analog; resists deamination and phosphorolysis |
| CPX-351 | Liposomal daunorubicin and cytarabine in a fixed 1:5 ratio |
| Lurbinectidin (PM01183) | Synthetic tetrahydroisoquinoline alkaloid DNA minor groove covalent binder |
| Vosaroxin (SNS-595) | Quinolone derivative; replication-dependent DNA damage agent |
| Immunomodulatory and immunosuppressive agents | |
| ALT-803 | Interleukin (IL)-15 superagonist mutant and a dimeric IL-15 receptor αSu/Fc fusion protein |
| DEC-205/NY-ESO-1 fusion protein CDX-1401 | Immunostimulator (DEC=endocytic dendritic cell receptor; NY-ESO-1 is a tumor associated antigen) |
| Equine antithymocyte globulin | T cell inhibition by polyclonal antibodies raised in animals |
| Ipilimumab (MDX-101) | Cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor |
| MK-3475 | Anti-programmed death 1 (PD1) antibody |
| Pomalidomide (CC4047) | Immunomodulatory agent with diverse activities; modulation of cereblon E3 ubiquitin ligase activity |
| Sirolimus | Mammalian target of rapamycin (mTOR) inhibitor |
| Temsirolimus | Mammalian target of rapamycin (mTOR) inhibitor |
| Apoptosis modulation | |
| ACE-536 | Transforming growth factor β (TGFβ) superfamily ligand trap |
| APG101 | CD95-Fc fusion protein (inhibits Fas signaling) |
| Birinapant (TL32711) | Peptidomimetic of second mitochondrial-derived activator of caspases (SMAC) and inhibitor of inhibitor of apoptosis protein (IAP) family proteins |
| LY2157299 | Transforming growth factor β (TGFβ) receptor I (TβRI) inhibitor |
| Sotatercept (ACE-011) | Soluble fusion protein: extracellular domain of activin receptor type IIA (ActRIIA) linked to the Fc protein of human IgG1; transforming growth factor β (TGFβ) pathway inhibitor |
| Miscellaneous | |
| Bortezomib | Proteasome inhibition |
| Brentuximab vedotin | Antibody against CD30 conjugated to a cytotoxin |
| CLT-008 | Human myeloid progenitor cells |
| CWP232291 | Inhibits Src associated in mitosis of 68 kDa (Sam68) protein |
| E7070 | Synthetic sulfonamide cell cycle inhibitor |
| Eltrombopag | Small molecule agonist of thrombopoietin receptor c-Mpl (i.e., thrombopoiesis stimulating agent) |
| Ganetespib (STA-9090) | Heat shock protein 90 (Hsp90) inhibitor |
| GSK525762 | Bromodomain and extra-terminal (BET) family inhibitor |
| Omacetaxine (homoharringtonine) | Protein translation inhibition |
| OXi4503 (combretastatin A1 diphosphate / CA1P) | Vascular disrupting agent |
| PF-04449913 | Hedgehog pathway inhibitor |
| Plerixafor (AMD3100) | Inhibition of C-X-C chemokine receptor type 4 (CXCR4) |
| PRI-724 | Modulator of Wnt signaling that inhibits the cAMP response element-binding protein (CREB) binding protein and β-catenin interaction |
| Vismodegib (GDC-0449) | Antagonist of smoothened receptor (SMO) in Hedgehog pathway |
| Agent (synonyms) . | Putative mechanism . |
|---|---|
| Kinase inhibitors | |
| INCB047986 | Janus-associated kinase (JAK) inhibitor |
| KB004 | Antibody against ephrin A3 (EphA3) receptor tyrosine kinase |
| LGH447 | Pim kinase inhibitor |
| MEK 162 | Inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2) |
| Midostaurin (PKC412) | Protein kinase C (PKC) inhibitor |
| PD-616 (12-O-tetradecanoylphorbol-13-acetate) | Protein kinase C (PKC) inhibitor |
| Quizartinib (AC220) | Fms-like tyrosine kinase 3 (FLT3) inhibitor |
| Rigosertib (SyB C-1101, SyB L-1101, ON 01910.Na) | Phosphoinositide-3 (PI3) kinase inhibitor, Polo-like kinase pathway inhibitor |
| Ruxolitinib (INCB18424) | Janus-associated kinase (JAK) inhibitor |
| Sorafenib | Inhibition of Raf, vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), Fms-like tyrosine kinase 3 (FLT3) and other kinases |
| Volasertib (BI 6727) | Polo-like kinase 1 (PLK1) inhibitor |
| ziv-Aflibercept | Vascular endothelial growth factor (VEGF) inhibitor |
| Deacetylase inhibitors and DNA methyltransferase inhibitors | |
| Oral azacitidine (CC-486) | DNA methyltransferase inhibitor |
| Oral decitabine and E7727 (ASTX727) | DNA methyltransferase inhibitor combined with cytidine deaminase inhibitor |
| SGI-110 | Nucleoside analog with DNA methyltransferase inhibitory activity |
| Mocetinostat (MGCD0103) | Deacetylase inhibitor |
| Panobinostat (LBH-589) | Deacetylase inhibitor |
| Pracinostat (SB939) | Deacetylase inhibitor |
| Vorinostat (suberanilohydroxamic acid, SAHA) | Deacetylase inhibitor |
| Altered cell metabolism | |
| AG-120, AG-221 | Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) inhibitors |
| Coenzyme Q10 and l-carnitine | Alteration of intracellular metabolism and electron transport chain |
| CPI613 | Inhibition of pyruvate dehydrogenase and ketoglutarate dehydrogenase |
| INCB024360 | Indoleamine 2,3-dioxygenase (IDO1) inhibitor |
| Cytotoxic agents/cell cycle inhibitors | |
| Cladribine (2-CDA) | Nucleoside analog |
| Clofarabine | Nucleoside analog; resists deamination and phosphorolysis |
| CPX-351 | Liposomal daunorubicin and cytarabine in a fixed 1:5 ratio |
| Lurbinectidin (PM01183) | Synthetic tetrahydroisoquinoline alkaloid DNA minor groove covalent binder |
| Vosaroxin (SNS-595) | Quinolone derivative; replication-dependent DNA damage agent |
| Immunomodulatory and immunosuppressive agents | |
| ALT-803 | Interleukin (IL)-15 superagonist mutant and a dimeric IL-15 receptor αSu/Fc fusion protein |
| DEC-205/NY-ESO-1 fusion protein CDX-1401 | Immunostimulator (DEC=endocytic dendritic cell receptor; NY-ESO-1 is a tumor associated antigen) |
| Equine antithymocyte globulin | T cell inhibition by polyclonal antibodies raised in animals |
| Ipilimumab (MDX-101) | Cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor |
| MK-3475 | Anti-programmed death 1 (PD1) antibody |
| Pomalidomide (CC4047) | Immunomodulatory agent with diverse activities; modulation of cereblon E3 ubiquitin ligase activity |
| Sirolimus | Mammalian target of rapamycin (mTOR) inhibitor |
| Temsirolimus | Mammalian target of rapamycin (mTOR) inhibitor |
| Apoptosis modulation | |
| ACE-536 | Transforming growth factor β (TGFβ) superfamily ligand trap |
| APG101 | CD95-Fc fusion protein (inhibits Fas signaling) |
| Birinapant (TL32711) | Peptidomimetic of second mitochondrial-derived activator of caspases (SMAC) and inhibitor of inhibitor of apoptosis protein (IAP) family proteins |
| LY2157299 | Transforming growth factor β (TGFβ) receptor I (TβRI) inhibitor |
| Sotatercept (ACE-011) | Soluble fusion protein: extracellular domain of activin receptor type IIA (ActRIIA) linked to the Fc protein of human IgG1; transforming growth factor β (TGFβ) pathway inhibitor |
| Miscellaneous | |
| Bortezomib | Proteasome inhibition |
| Brentuximab vedotin | Antibody against CD30 conjugated to a cytotoxin |
| CLT-008 | Human myeloid progenitor cells |
| CWP232291 | Inhibits Src associated in mitosis of 68 kDa (Sam68) protein |
| E7070 | Synthetic sulfonamide cell cycle inhibitor |
| Eltrombopag | Small molecule agonist of thrombopoietin receptor c-Mpl (i.e., thrombopoiesis stimulating agent) |
| Ganetespib (STA-9090) | Heat shock protein 90 (Hsp90) inhibitor |
| GSK525762 | Bromodomain and extra-terminal (BET) family inhibitor |
| Omacetaxine (homoharringtonine) | Protein translation inhibition |
| OXi4503 (combretastatin A1 diphosphate / CA1P) | Vascular disrupting agent |
| PF-04449913 | Hedgehog pathway inhibitor |
| Plerixafor (AMD3100) | Inhibition of C-X-C chemokine receptor type 4 (CXCR4) |
| PRI-724 | Modulator of Wnt signaling that inhibits the cAMP response element-binding protein (CREB) binding protein and β-catenin interaction |
| Vismodegib (GDC-0449) | Antagonist of smoothened receptor (SMO) in Hedgehog pathway |
Inclusion in this table is based on review of clinicaltrials.gov website April 16, 2014, with search term “myelodysplastic syndrome,” restricted to “Open” trials. Agents are included if (1) the study in which they were being tested had been updated or verified since January 1, 2012, and was either in “Recruiting” or “Not Yet Recruiting” status and were excluded if they were “Completed,” “Unknown,” or “Terminated”; (2) they do not involve a drug already FDA approved for MDS (lenalidomide, azacitidine, and decitabine), AML, or for an iron chelation indication; (3) they are not for stem cell transplant conditioning, cellular product manipulation, graft versus host prevention or treatment, or a vaccine. Many trials of these agents, especially early phase studies, were also enrolling patients with AML or other hematological malignancies.