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  1. Curcumin has antitumor and anti-inflammatory effects, and has been reported to exert therapeutic effects in various animal pathological models. However, since it is poorly soluble in water and has extremely poor absorption into the living body, it is difficult to apply it to humans because a special dosing method is used in animal experiments.

  2. TBP1901 is a sodium salt in which glucuronic acid is bound to curcumin and is a novel substance. It can be injected with the highly water-soluble curcumin prodrug.

  3. TBP1901 is converted to curcumin by β-glucuronidase in vivo. A blood concentration close to 1000 times that of oral administration of curcumin can be obtained.

  4. Since TBP1901 is converted to curcumin by β-glucuronidase activated in cancer tissues and inflamed sites and shows medicinal effects, it can be expected as a highly safe drug with little effect on normal tissues. In addition, it has been confirmed that curcumin is present in cancer tissues for a long time after administration of TBP1901, and it can be an anticancer drug having a tumor-specific action.

​Target disease

1. Anti-cancer drug

  • Multiple myeloma

  • Glioblastoma

  • Colorectal cancer

2. Prevention and treatment of infectious diseases

  • COVID-19

  • Cytokine release syndrome

3. Osteoarthritis of the knee

1. ​Anti-cancer agent

​・ Multiple myeloma (bortezomib resistance)

The annual number of cases of multiple myeloma in Japan will be about 8,200 in 2020, and the number of cases has doubled in the last 20 years. Bortezomib, a proteasome inhibitor, is widely used as a key drug for multiple myeloma, but treatment resistance develops over time in 70-80% of patients. Although the development of new anticancer drugs for multiple myeloma has been remarkable in recent years, it has become refractory to treatment over time, and it is still difficult to aim for cure. In addition, since these new anticancer drugs also have serious side effects such as infectious diseases, it is often difficult to administer the new drugs to patients with multiple myeloma whose average age at diagnosis is over 70 years old. Therefore, it is desired to develop a new anticancer drug that is less likely to cause treatment resistance and has few side effects.

1 x 107 KMS11 / BTZ (bortezomib-resistant multiple myeloma cell lines) were transplanted subcutaneously into NOD Scid mice (female 6 weeks old), and drug administration was started 2 weeks after transplantation (Day 0). Bortezomib was administered intraperitoneally on a schedule of 1 mg / kg twice / week and TBP1901 at 30 mg / kg and 90 mg / kg 3 times / week.

As a result, it was revealed that bortezomib showed almost no antitumor effect, but TBP1901 regressed the tumor in a dose-dependent manner.

​・ Glioblastoma

It is estimated that about 20,000 new cases of brain tumors occur every year in Japan, and glioblastoma  Occupies about 2,500 of them. Glioblastoma is one of the most malignant cancers, with a 5-year survival rate of around 15%. The standard treatment for glioblastoma is a combination of temozolomide and radiation for tumor removal, but complete surgical removal is not possible, and many tumors are refractory to treatment, eventually leading to death in all cases. In chemotherapy, the drug must cross the blood-brain barrier, and the drugs that are effective for glioblastoma are extremely limited, and new drugs are desired.

Joint research with the National Cancer Center

When TBP1901 was administered to stereotactic brain transplanted mice of the glioblastoma cell line (U87) on Day 7-28 and the survival time from there was compared, the survival time (median) of the control group was 32 days, and the low concentration TBP1901 The group had 39 days and the high-concentration TBP1901 group had 59 days, with TBP1901 prolonging survival and its effects were concentration-dependent. In the high concentration group, 25% of the animals survived for more than 80 days.

​・ Colorectal cancer (Oxaliplatin resistance)

Large-scale clinical studies have reported that the KRAS mutation found in about 40% of colorectal cancers is a poor prognostic factor for the oxaliplatin regimen, a key drug in colorectal cancer. Colorectal cancer with KRAS mutation cannot be expected to have an anti-EGFR antibody effect, and is also resistant to oxaliplatin as compared with the wild type, so development of a new treatment method is required.

The HCT116 / p53 + Kras double mutant cell line was transplanted subcutaneously into nude mice (female 6 weeks old), and drug administration was started 2 weeks after transplantation (Day 0). Oxaliplatin was administered intraperitoneally at a schedule of 8 mg / kg twice / week and TBP1901 at 90 mg / kg 3 times / week.

As a result, in a cancer-bearing animal experiment using an oxaliplatin-resistant cell line, oxaliplatin showed almost no antitumor effect, but TBP1901 showed a remarkable growth inhibitory effect.

Our published paper

Curcumin β-D-glucuronide Exhibits Anti-Tumor Effects on Oxaliplatin-Resistant Colon Cancer With Less Toxicity in Vivo. Cancer Sci.2020 May; 111 (5): 1785-1793

2. Infectious disease prevention / treatment

​・ COVID-19

Joint research with the National Institute of Infectious Diseases

SARS-CoV-2 has been shown to invade cells via TMPRSS2. Therefore, when SARS-CoV-2 was infected with TMPRSS2-expressing VeroE6 cells, it was revealed that curcumin suppresses viral growth. Its EC50 was 25 μM, indicating that curcumin has the same SARS-CoV-2 infection-inhibiting effect as existing and under-development drugs.

SARS-CoV-2 infection inhibitory effect of existing drugs


  • Favipiravir (Abigan): EC50 64 μM or higher

  • Remdesivir: EC50 10 μM or less

  • Fusan: EC50 32 μM

​・ Cytokine release syndrome

With COVID-19, more than 80% of patients are asymptomatic to mild, but 15% are moderate to severe with cough and shortness of breath, and 3% require intensive care. Not only for COVID-19, but also for emerging and re-emerging infectious diseases, it has come to be recognized that it is important to prevent the aggravation of secondary patients and stop the collapse of medical care. Like other viral pneumonia, cytokine release syndrome (cytokine storm) is thought to play a central role in the aggravation of COVID-19. At present, steroids and anti-IL6 antibodies have been administered to cytokine storms, and although certain effects have been obtained, it is difficult to say that they have achieved sufficient effects, and more effective drugs are desired. ..

[Left figure] Suppression of LPS-induced lethality by TBP1901. All patients died in the LPS-treated group in 2 days, whereas the LPS + TBP1901-treated group significantly increased the survival rate.

[Middle figure] TBP1901 significantly suppressed the TNFα protein concentration in blood by treatment before LPS administration (preventive effect).

[Right figure] 0.5 hours after LPS administration, even if TBP1901 was administered when TNFα secretion was already enhanced (post-administration), the TNFα protein concentration in the blood was significantly suppressed (therapeutic effect).

Can be an effective drug for both prevention and treatment of cytokine storm aggravation

3. Osteoarthritis of the knee

Direct injection of TBP1901 into the knee of osteoarthritis confirmed that TBP1901 significantly suppressed OA syndrome in an in vivo study using knee osteoarthritis (OA) model animals.



Safranin-O / fast-green image and OA score (Tibia)

OARSI score P <0.01

CMG can suppress OA in Tibia at 10th week

Subchondral bone (SB) Cysts and osteophyte volume

P <0.01 in both.

CMG can suppress the cysts in SB at 10th week.

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