| Identification |
| Chemical Name |
Bortezomib |
| Accession Number |
HAMDB632 |
| Alternative Names |
Not Available |
| IUPAC Name |
[(1R)-3-methyl-1-[[(2S)-3-phenyl-2-(pyrazine-2-carbonylamino)propanoyl]amino]butyl]boronic acid |
| Formula |
B(C(CC(C)C)NC(=O)C(CC1=CC=CC=C1)NC(=O)C2=NC=CN=C2)(O)O |
| Canonical SMILES |
B(C(CC(C)C)NC(=O)C(CC1=CC=CC=C1)NC(=O)C2=NC=CN=C2)(O)O |
| Structure |
C)NC(=O)C(CC1=CC=CC=C1)NC(=O)C2=NC=CN=C2)(O)O/PNG)
|
| Physicochemical Properties |
| Molecular Weight |
384.240Molecular weight |
| Hbond Donor |
4Number of hydrogen bond acceptor atoms
(not counting acidic atoms but counting atoms that are both hydrogen bond donors and acceptors such as -OH).
|
| Hbond Acceptor |
6
Number of hydrogen bond donor atoms (not counting basic atoms but counting atoms that are both hydrogen bond donors and acceptors such as -OH).
|
| logP (o/w) |
0.951
Log of the octanol/water partition coefficient (including implicit hydrogens). [LOGP 1998]
|
| logS |
-2.186
Log of the aqueous solubility (mol/L).
|
| MR |
11.025
Molecular refractivity (including implicit hydrogens).
|
| SlogP |
0.361
Log of the octanol/water partition coefficient. [Crippen 1999]
|
| TPSA |
124.440
Polar surface area (Å2) calculated using group contributions to approximate the polar surface area from connection table information only. The parameterization is that of Ertl et al. [Ertl 2000].
|
| logD (PH=7) |
3.136
The octanol/water distribution coefficient at pH 7.
|
| pKa (PH=7) |
3.946
The pKa of the reaction that removes a proton from the ensemble of states with a hydrogen count equal to the input structure.
|
| pKb (PH=7) |
14.000
The pKb of the reaction that adds a proton from the ensemble of states with a hydrogen count equal to the input structure.
|
| Lipinski druglike |
1
One if and only if lip_violation < 2 otherwise zero.
|
| Solubility |
Soluble in DMSO > 10 mM |
| Role in Autophagy |
|
5 related item(s)
1. bortezomib |
| Chemical Name |
bortezomib |
| Relationship with Autophagy |
increased activity of bortezomib increases autophagy of colorectal cancer cell lines
|
| Mutation Evidence
|
wild type |
| Biomarker Application
|
not applicable |
| Species Evidence
|
Human |
| Drug Target Evidence
|
not applicable |
| Expression Evidence
|
not applicable |
| Causal or Correlated
|
causal |
| Findings |
5 |
References
- Ding Wx, Ni Hm, Gao W, Yoshimori T, Stolz Db, Ron D, Yin Xm, Linking Of Autophagy To Ubiquitin-proteasome System Is Important For The Regulation Of Endoplasmic Reticulum Stress And Cell Viability., Am J Pathol.2007 Aug;171(2):513-24. [PMID:17620365 ]
2. bortezomib |
| Chemical Name |
bortezomib |
| Relationship with Autophagy |
increased activity of bortezomib increases autophagy by bone marrow cells
|
| Mutation Evidence
|
wild type |
| Biomarker Application
|
not applicable |
| Species Evidence
|
Mouse |
| Drug Target Evidence
|
not applicable |
| Expression Evidence
|
not applicable |
| Causal or Correlated
|
causal |
| Findings |
1 |
References
- Khandros E, Thom Cs, D'souza J, Weiss Mj, Integrated Protein Quality-control Pathways Regulate Free ��-globin In Murine ��-thalassemia., Blood.2012 May 31;119(22):5265-75. Doi: 10.1182/blood-2011-12-397729. [PMID:22427201 ]
3. bortezomib |
| Chemical Name |
bortezomib |
| Relationship with Autophagy |
increased activity of bortezomib increases autophagy of breast cancer cell lines
|
| Mutation Evidence
|
wild type |
| Biomarker Application
|
not applicable |
| Species Evidence
|
Uncategorized |
| Drug Target Evidence
|
not applicable |
| Expression Evidence
|
not applicable |
| Causal or Correlated
|
causal |
| Findings |
3 |
References
- Verfaillie T, Salazar M, Velasco G, Agostinis P, Linking Er Stress To Autophagy: Potential Implications For Cancer Therapy., Int J Cell Biol.2010;2010:930509. Doi: 10.1155/2010/930509. [PMID:20145727 ]
4. bortezomib |
| Chemical Name |
bortezomib |
| Relationship with Autophagy |
increased activity of bortezomib increases autophagy of fibroblasts
|
| Mutation Evidence
|
wild type |
| Biomarker Application
|
not applicable |
| Species Evidence
|
Uncategorized |
| Drug Target Evidence
|
not applicable |
| Expression Evidence
|
not applicable |
| Causal or Correlated
|
causal |
| Findings |
3 |
References
- Ding Wx, Ni Hm, Gao W, Yoshimori T, Stolz Db, Ron D, Yin Xm, Linking Of Autophagy To Ubiquitin-proteasome System Is Important For The Regulation Of Endoplasmic Reticulum Stress And Cell Viability., Am J Pathol.2007 Aug;171(2):513-24. [PMID:17620365 ]
5. bortezomib |
| Chemical Name |
bortezomib |
| Relationship with Autophagy |
increased activity of bortezomib increases autophagy of fibroblast cell lines
|
| Mutation Evidence
|
wild type |
| Biomarker Application
|
not applicable |
| Species Evidence
|
Mouse |
| Drug Target Evidence
|
not applicable |
| Expression Evidence
|
not applicable |
| Causal or Correlated
|
causal |
| Findings |
2 |
References
- Fontanini A, Foti C, Potu H, Crivellato E, Maestro R, Bernardi P, Demarchi F, Brancolini C, The Isopeptidase Inhibitor G5 Triggers A Caspase-independent Necrotic Death In Cells Resistant To Apoptosis: A Comparative Study With The Proteasome Inhibitor Bortezomib., J Biol Chem.2009 Mar 27;284(13):8369-81. Doi: 10.1074/jbc.m806113200. [PMID:19139105 ]
|
| Biological Behaviors |
| Gene Name |
26s-proteasome |
| Target |
Proteasome |
| Pathway |
- Ubiquitination
|
| Biological Description |
Proteasome Inhibitor |
| Research Area |
Cancer |
| Category |
Proteasome Inhibitor |
| In Vitro |
Bortezomib potently suppressed the growth in 21 drugs, while other compounds had no or minimal effect on cell growth. We thus focused on bortezomib and examined its growth inhibitory properties against nine canine malignant melanoma cell lines (CMM-1, CMM-2, ChMC, KMeC, LMeC, OMJ, OMS, OMK, and NML). Bortezomib inhibited the growth of all cell lines with calculated IC50 values of 3.5~5.6 nM. |
| In Vivo |
The in vivo growth inhibitory activity of bortezomib against CMM-1 cells was evaluated using a xenograft mouse model. Bortezomib significantly suppressed the growth of tumours after Day 4 of treatment (P < 0.01, control vs. bortezomib). Tumours from the bortezomib-treated mice showed a significant decrease in mitotic index compared to controls (P<0.01). Similarly, the Ki67 index was significantly decreased in tumours excised from the bortezomib-treated mice when compared to controls (P < 0.01). |
| Clinical Trial |
Not Available |
| External Links |
| CAS Numbers |
179324-69-7 |
| Pubchem |
387447 |
| HMDB |
HMDB14334 |
| DrugBank |
DB00188 |
| References |
- Ito K, Kobayashi M, Kuroki S, Sasaki Y, Iwata T, Mori K, Kuroki T, Ozawa Y, Tetsuka M, Nakagawa T, Hiroi T, Yamamoto H, Ono K, Washizu T, Bonkobara M, The Proteasome Inhibitor Bortezomib Inhibits The Growth Of Canine Malignant Melanoma Cells In Vitro And In Vivo., Vet J.2013 Dec;198(3):577-82. Doi: 10.1016/j.tvjl.2013.08.003. [PMID:24035468 ]
|
