PHGDH Inhibitor
BI-4916
BI-4916 is an ester prodrug of the highly potent PHGDH inhibitor BI-4924. In contrast to BI-4924, BI-4916 is cell permeable, undergoing cellular uptake followed by hydrolysis to BI-4924. This allows for it to be used as intracellular enrichment of BI-4916. The negative control BI-5583 is also provided. Both compounds should be only used to perform cellular experiments.
More information
PHGDH (3-phosphoglycerate dehydrogenase) catalyzes the first step of de novo serine biosynthesis downstream of glycolysis and is the rate limiting enzyme for the pathway. PHGDH converts 3-phosphoglycerate (3-PG) to 3-phosphohydroxypyruvate (3-PHP) in a NAD-dependent manner. PHGDH is amplified or overexpressed in a subset of tumors, most frequently melanoma and triple-negative breast cancers. Cells with amplified or overexpressed PHGDH show an elevated serine synthesis and are relatively resistant to serine starvation while showing some dependency on PHGDH activity.
BI-4924 bound to PHGDH (PDB code: 6RJ6)
| Probe name / negative control | BI-4916 | BI-5583 |
| MW [Da, free base]a | 527.4 | 372.8 |
| NAD+ high assay (250 µM) (IC50) [nM] | 169b | n.d. |
| PHGDH SPR [µM] | n.a. | 28.4 |
| 13C-Serine; 72 h (IC50) [nM] | 2,032 | n.a. |
a For the salt form you will get, please refer to the label on the vial and for the molecular weight of the salt, please refer to the FAQs
b The chemical stability of the tosyl acetate ester was found to be limited under the assay conditions – It is highly likely that all activity in the biochemical assay results from the formation of the carboxylic acid analog BI-4924 which is also available on opnMe.com
cAll assay conditions are in reference 1
| Probe name / negative control | BI-4916 | BI-5583 |
| logP @ pH 11 | 5.6 | n.a. |
| Solubility @ pH 6.8 [µg/mL] | <1 | >87 |
| Caco-2 permeability AB @ pH 7.4 [*10-6 cm/s] | n.d. | <1.8 |
| Caco-2 efflux ratio | n.d. | n.a. |
| Microsomal stability (human/rat) [% QH] | n.d. | 24 / <23 |
| Plasma Protein Binding (10% FCS) [%] | 98.8 | Ongoing |
| CYP 3A4 (IC50) [µM] | >50 | >50 |
| CYP 2C8 (IC50) [µM] | 39.0 | >50 |
| CYP 2C9 (IC50) [µM] | >50 | >50 |
| CYP 2C19 (IC50) [µM] | >50 | >50 |
| CYP 2D6 (IC50) [µM] | >50 | >50 |
BI-5583 which serves as a negative control
The SafetyScreen44™ panel has been measured (@10 µM) for BI-4916, and for 3/44 proteins > 70% CTRL inhibition was found: CCKA (82%), 5HT2B (94%), ALPHA2A (101%).
| SELECTIVITY DATA AVAILABLE | BI-4916 | BI-5583 |
SafetyScreen44™ with kind support of  | Yes | Yes |
| Invitrogen® | No | Yes |
| DiscoverX® | No | No |
| Dundee | No | No |
Download selectivity data:
BI-4916_selectivityData.xlsx
BI-5583_selectivityData_0.xlsx
BI-4924 (active form of prodrug BI-4916) bound to PHGDH (PDB code: 6RJ6)
Other PHGDH inhibitors have been described in literature2.
BI-4916 is the ester prodrug of BI-4924, a highly potent inhibitor of PHGDH with good selectivity. We also provide the negative control BI-5583.
The ester prodrug BI-4916 should be used to perform cellular experiments.
Intracellular trapping of the selective phosphoglycerate dehydrogenase (PHGDH) inhibitor BI-4916 disrupts serine biosynthesis
Weinstabl H., Treu M., Rinnenthal J., Zahn S. K., Ettmayer P., Bader G., Dahmann G., Kessler D., Rumpel K., Mischerikow N., Savarese F., Gerstberger T., Mayer M., Zoephel A., Schnitzer R., Sommergruber W., Martinelli P., Arnhof H., Peric-Simov B., Hofbauer K. S., Garavel G., Scherbantin Y., Mitzner S., Fett T. N., Scholz G., Bruchhaus J., Burkard M., Kousek R., Ciftci T., Sharps B., Schrenk A., Harrer C., Haering D., Wolkerstorfer B., Zhang X., Lv X., Du A., Li D., Li Y., Quant J., Pearson M., McConnell D. B.
J. Med. Chem. 2019, 62, 7976–7997.
Functional Genomics Reveal that the Serine Synthesis Pathway is Essential in Breast Cancer
Possemato R., Marks K. M., Shaul Y. D., Pacold M. E., Kim D., Birsoy K., Sethumadhavan S., Woo H.-K., Jang H. G., Jha A. K., Chen W. W., Barrett F. G., Stransky N., Tsun Z.-Y., Cowley G. S., Barretina J., Kalaany N. Y., Hsu P. P., Ottina K., Chan A. M., Yuan B., Garraway L. A., Root D. E., Mino-Kenudson M., Brachtel E. F., Driggers E. M., Sabatini D. M.
Nature 2011, 476, 346.
Phosphoglycerate Dehydrogenase Diverts Glycolytic Flux and Contributes to Oncogenesis
Locasale J. W., Grassian A. R., Melman T., Lyssiotis C. A., Mattaini K. R., Bass A. J., Heffron G., Metallo C. M., Muranen T., Sharfi H., Sasaki A. T., Anastasiou D., Mullarky E., Vokes N. I., Sasaki M., Beroukhim R., Stephanopoulos G., Ligon A. H., Meyerson M., Richardson A. L., Chin L., Wagner G., Asara J. M., Brugge J. S., Cantley L. C., Vander Heiden M. G.
Nat. Genet. 2011, 43, 869.
When you plan a publication, please use the following acknowledgement:
BI-4916 was kindly provided by Boehringer Ingelheim via its open innovation platform opnMe, available at https://www.opnme.com.