NPASS Compound

Structure

NPC206712 OpenBabel06302215372D 42 42 0 0 1 0 0 0 0 0999 V2000 10.9899 -5.4040 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 11.5776 -4.5949 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 11.1709 -3.6814 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 11.7587 -2.8724 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.1764 -3.5769 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 9.7696 -2.6633 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.3574 -1.8543 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 8.7751 -2.5588 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 8.3684 -1.6452 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 8.9562 -0.8362 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5494 0.0773 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1372 0.8863 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5549 0.1818 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3739 -1.5407 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9671 -0.6272 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 5.9726 -0.5226 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 5.5659 0.3909 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1537 1.1999 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7469 2.1135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1482 1.0954 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3848 -1.3317 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3903 -1.2271 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.9836 -0.3136 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.5714 0.4954 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9890 -0.2091 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5823 0.7045 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5878 0.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1810 1.7226 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0000 -0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.3090 -0.9511 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.2601 -1.2601 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 -1.5388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3090 -0.9511 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5878 0.8090 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 -2.5388 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3660 -3.0388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7916 -2.2452 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7861 -2.3497 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 9.5886 -4.3859 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 8.5941 -4.2814 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.9953 -5.2994 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 2 3 1 0 0 0 0 3 4 1 1 0 0 0 3 5 1 0 0 0 0 5 6 1 6 0 0 0 5 40 1 0 0 0 0 6 7 2 0 0 0 0 6 8 1 0 0 0 0 8 9 1 0 0 0 0 9 10 1 6 0 0 0 9 14 1 0 0 0 0 10 11 1 0 0 0 0 11 12 1 0 0 0 0 11 13 1 0 0 0 0 14 15 2 3 0 0 0 14 39 1 0 0 0 0 15 16 1 0 0 0 0 16 17 1 6 0 0 0 16 21 1 0 0 0 0 17 18 1 0 0 0 0 18 19 1 0 0 0 0 18 20 1 0 0 0 0 21 22 2 3 0 0 0 21 38 1 0 0 0 0 22 23 1 0 0 0 0 23 24 1 6 0 0 0 23 25 1 0 0 0 0 25 26 2 0 0 0 0 26 27 1 0 0 0 0 27 28 2 0 0 0 0 27 29 1 0 0 0 0 29 34 1 0 0 0 0 29 30 1 0 0 0 0 30 31 1 1 0 0 0 30 32 1 0 0 0 0 32 33 2 0 0 0 0 32 36 1 0 0 0 0 33 34 1 0 0 0 0 34 35 2 0 0 0 0 36 37 1 0 0 0 0 40 41 1 0 0 0 0 40 42 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	312.14
Volume:	328.216
LogP:	4.346
LogD:	3.689
LogS:	-5.925
# Rotatable Bonds:	5
TPSA:	51.83
# H-Bond Aceptor:	4
# H-Bond Donor:	1
# Rings:	3
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.775
Synthetic Accessibility Score:	2.152
Fsp3:	0.263
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.826
MDCK Permeability:	2.777780537144281e-05
Pgp-inhibitor:	0.992
Pgp-substrate:	0.411
Human Intestinal Absorption (HIA):	0.004
20% Bioavailability (F20%):	0.003
30% Bioavailability (F30%):	0.01

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.521
Plasma Protein Binding (PPB):	96.66554260253906%
Volume Distribution (VD):	0.617
Pgp-substrate:	4.1378254890441895%

ADMET: Metabolism

CYP1A2-inhibitor:	0.943
CYP1A2-substrate:	0.958
CYP2C19-inhibitor:	0.804
CYP2C19-substrate:	0.165
CYP2C9-inhibitor:	0.653
CYP2C9-substrate:	0.919
CYP2D6-inhibitor:	0.437
CYP2D6-substrate:	0.94
CYP3A4-inhibitor:	0.772
CYP3A4-substrate:	0.464

ADMET: Excretion

Clearance (CL):	10.242
Half-life (T1/2):	0.216

ADMET: Toxicity

hERG Blockers:	0.023
Human Hepatotoxicity (H-HT):	0.339
Drug-inuced Liver Injury (DILI):	0.951
AMES Toxicity:	0.462
Rat Oral Acute Toxicity:	0.052
Maximum Recommended Daily Dose:	0.587
Skin Sensitization:	0.267
Carcinogencity:	0.489
Eye Corrosion:	0.004
Eye Irritation:	0.362
Respiratory Toxicity:	0.028

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC206712

Natural Product ID:	NPC206712
*Common Name:**	ASRBKZHDORPEHO-KYJIWOQOSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	ASRBKZHDORPEHO-KYJIWOQOSA-N
Standard InCHI:	InChI=1S/C31H52N4O7/c1-12-20(6)28(34(9)10)31(40)42-25(16-19(4)5)30(39)33-23(15-18(2)3)29(38)32-21(7)13-14-26(36)35-22(8)24(41-11)17-27(35)37/h13-14,17-23,25,28H,12,15-16H2,1-11H3,(H,32,38)(H,33,39)/b14-13+/t20-,21-,22-,23-,25-,28-/m0/s1
SMILES:	CC[C@H](C)[C@@H](C(=O)O[C@@H](CC(C)C)C(=N[C@@H](CC(C)C)C(=N[C@@H](C)/C=C/C(=O)N1[C@@H](C)C(=CC1=O)OC)O)O)N(C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	25209862
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0001813] Peptidomimetics [CHEMONTID:0001961] Depsipeptides

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO40741	Cyanobacteria spp.	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[19161344]

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	28
Ki	1
LD50	2
Others	8

Activity Type	# Activity
Cell Line	11
Individual Protein	17
Organism	5
Others	6

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT189	Cell Line	Vero	Chlorocebus aethiops	TC50	=	10.4	uM	PMID[19161344]
NPT469	Individual Protein	Cathepsin L	Homo sapiens	Ki	=	9000.0	/M/s	PMID[24364476]
NPT469	Individual Protein	Cathepsin L	Homo sapiens	Inhibition	=	12.0	%	PMID[24364476]
NPT5085	Individual Protein	Cathepsin H	Homo sapiens	IC50	>	30000.0	nM	PMID[24364476]
NPT214	Individual Protein	Cathepsin B	Homo sapiens	IC50	=	1700.0	nM	PMID[24364476]
NPT214	Individual Protein	Cathepsin B	Homo sapiens	IC50	=	4200.0	nM	PMID[24364476]
NPT601	Individual Protein	Cathepsin L2	Homo sapiens	IC50	=	140.0	nM	PMID[24364476]
NPT601	Individual Protein	Cathepsin L2	Homo sapiens	IC50	=	460.0	nM	PMID[24364476]
NPT469	Individual Protein	Cathepsin L	Homo sapiens	IC50	=	5.0	nM	PMID[24364476]
NPT469	Individual Protein	Cathepsin L	Homo sapiens	IC50	=	47.0	nM	PMID[24364476]
NPT3939	Individual Protein	Falcipain 2	Plasmodium falciparum	IC50	=	8.5	nM	PMID[25412465]
NPT3722	Cell Line	4T1	Mus musculus	IC50	=	34600.0	nM	PMID[30006166]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	IC50	=	34900.0	nM	PMID[30006166]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	45500.0	nM	PMID[30006166]
NPT139	Cell Line	HT-29	Homo sapiens	IC50	=	53000.0	nM	PMID[30006166]
NPT1083	Cell Line	A-375	Homo sapiens	IC50	=	45600.0	nM	PMID[30006166]
NPT169	Cell Line	B16-F10	Mus musculus	IC50	=	59700.0	nM	PMID[30006166]
NPT461	Cell Line	PANC-1	Homo sapiens	IC50	=	31200.0	nM	PMID[30006166]
NPT81	Cell Line	A549	Homo sapiens	IC50	=	40400.0	nM	PMID[30006166]
NPT165	Cell Line	HeLa	Homo sapiens	IC50	=	12000.0	nM	PMID[30006166]
NPT469	Individual Protein	Cathepsin L	Homo sapiens	Activity	=	5.0	%	PMID[31539239]
NPT469	Individual Protein	Cathepsin L	Homo sapiens	Ratio	=	901.0	10'3/M/s	PMID[31539239]
NPT469	Individual Protein	Cathepsin L	Homo sapiens	IC50	=	4.67	nM	PMID[31539239]
NPT469	Individual Protein	Cathepsin L	Homo sapiens	IC50	=	5.0	nM	PMID[31539239]
NPT2219	Cell Line	C2C12	Mus musculus	LD50	>	10.0	uM	PMID[31539239]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	8400.0	nM	PMID[19161344]
NPT633	Organism	Leishmania donovani	Leishmania donovani	IC50	=	9300.0	nM	PMID[19161344]
NPT580	Organism	Trypanosoma cruzi	Trypanosoma cruzi	IC50	>	16900.0	nM	PMID[19161344]
NPT2	Others	Unspecified		Ratio IC50	=	320.0	n.a.	PMID[24364476]
NPT2	Others	Unspecified		Ratio IC50	=	91.0	n.a.	PMID[24364476]
NPT2	Others	Unspecified		Ratio IC50	=	28.0	n.a.	PMID[24364476]
NPT2	Others	Unspecified		Ratio IC50	=	10.0	n.a.	PMID[24364476]
NPT2	Others	Unspecified		IC50	=	22.0	nM	PMID[25412465]
NPT2	Others	Unspecified		IC50	=	140.0	nM	PMID[25412465]
NPT757	Organism	Plasmodium falciparum 3D7	Plasmodium falciparum 3D7	IC50	=	50.0	nM	PMID[25412465]
NPT580	Organism	Trypanosoma cruzi	Trypanosoma cruzi	LD50	=	14.7	nM	PMID[31539239]
NPT791	Individual Protein	Cruzipain	Trypanosoma cruzi	IC50	=	0.26	nM	PMID[31539239]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC206712 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	90
0.1-0.2	800
0.2-0.3	18313
0.3-0.4	18252
0.4-0.5	4389
0.5-0.6	719
0.6-0.7	114
0.7-0.8	19
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID

Chemically structural similarity: II. Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC206712 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	75
0.1-0.2	455
0.2-0.3	3787
0.3-0.4	3947
0.4-0.5	786
0.5-0.6	100
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage

Bioactivity similarity: Similar Natural Products in NPASS

Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.

Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data