Umbralisib

Umbralisib (development codes RP5264 and TGR 1202) is an experimental oral PI3K delta inhibitor.[1] It also inhibits CK1 epsilon.[2]

Umbralisib

Clinical data
Other names	RP5264; TGR 1202
Legal status
Legal status	Investigational
Identifiers
IUPAC name 2-[(1S)-1-[4-Amino-3-(3-fluoro-4-propan-2-yloxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-6-fluoro-3-(3-fluorophenyl)chromen-4-one
CAS Number	1532533-67-7
PubChem CID	72950888
UNII	38073MQB2A
Chemical and physical data
Formula	C31H24F3N5O3
Molar mass	571.560 g·mol^−1
3D model (JSmol)	Interactive image
SMILES C[C@@H](C1=C(C(=O)C2=C(O1)C=CC(=C2)F)C3=CC(=CC=C3)F)N4C5=NC=NC(=C5C(=N4)C6=CC(=C(C=C6)OC(C)C)F)N

It has undergone clinical studies for chronic lymphocytic leukemia (CLL).[3][4] Three year data (including follicular lymphoma and DLBCL) was announced June 2016.[5] It is in combination trials for various leukemias and lymphomas, such as mantle cell lymphoma (MCL)[6][7] and other lymphomas.[8]

The drug has been granted the FDA's breakthrough therapy status for use in patients with marginal zone lymphoma (MZL), a type of cancer with no specifically approved therapies.[9]

References

1. Clinical trial number NCT01767766 for "Evaluate the Safety and Efficacy of TGR 1202 in Patients With Relapsed or Refractory Hematologic Malignancies" at ClinicalTrials.gov
2. Barrientos JC (April 2018). "Can umbralisib bring PI3Kδ out of the shadows?". The Lancet. Oncology. 19 (4): 432–434. doi:10.1016/S1470-2045(18)30154-2. PMID 29475725.
3. Inman S (19 March 2016). "Novel BTK, PI3K Inhibitors on Horizon for Relapsed CLL". OncLive. Archived from the original on 1 May 2016.
4. "Therapy Focus –- TG Could Benefit From Zydelig Setback". Seeking Alpha. 29 March 2016.
5. "TG Therapeutics, Inc. Announces First Patient Enrolled in the Registration-Directed UNITY-DLBCL Phase 2b Trial". TG Therapeutics Inc. June 2016.
6. Clinical trial number NCT02268851 for "A Phase I/Ib Safety and Efficacy Study of the PI3K-delta Inhibitor TGR-1202 and Ibrutinib in Patients With CLL or MCL" at ClinicalTrials.gov
7. "Follow-Up Data for Combination of TGR-1202 (umbralisib) plus Ibrutinib in Patients with Relapsed or Refractory CLL and MCL". Globenewswire.com. 14 June 2017.
8. Clinical trial number NCT02793583 for "Study to Assess the Efficacy and Safety of Ublituximab + TGR-1202 With or Without Bendamustine and TGR-1202 Alone in Patients With Previously Treated Non-Hodgkin's Lymphoma (UNITY-NHL)" at ClinicalTrials.gov
9. Columbus G (22 January 2019). "FDA Grants Umbralisib Breakthrough Designation for Marginal Zone Lymphoma". OncLive. Archived from the original on 23 January 2019.

Further reading

• Barrientos JC (April 2018). "Can umbralisib bring PI3Kδ out of the shadows?". The Lancet. Oncology. 19 (4): 432–434. doi:10.1016/S1470-2045(18)30154-2. PMID 29475725.