NPASS Compound

Structure

NPC489055 OpenBabel06302215142D 60 63 0 0 1 0 0 0 0 0999 V2000 5.2221 7.9676 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5312 7.0165 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8620 6.2734 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5093 6.8086 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 6.8183 5.8576 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7965 5.6497 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1492 5.1144 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 5.1710 5.3223 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4582 4.1634 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 7.4364 3.9555 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1055 4.6986 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7454 3.0044 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7891 3.4202 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8109 3.6281 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0981 2.4692 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 7.0492 2.1602 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0492 1.1602 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0981 0.8511 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5103 1.6602 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.5103 1.6602 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0103 2.5262 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0103 0.7941 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 4.4170 -0.1194 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6739 -0.7885 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8079 -0.2885 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0158 0.6896 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.3467 1.4328 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6557 2.3838 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3685 1.2248 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6994 1.9680 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0084 2.9190 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9865 3.1270 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3393 3.6622 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2788 1.7601 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9479 2.5032 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5878 0.8090 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.5388 0.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3479 1.0878 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2614 0.6810 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3659 -0.3135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2795 -0.7202 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0885 -0.1324 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9840 0.8621 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0704 1.2688 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5388 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5878 -0.8090 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 1.0000 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3479 -1.0878 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2433 -2.0823 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1784 7.5518 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 6.8694 8.5028 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5385 9.2460 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 8.5167 9.0381 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8257 8.0870 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1858 9.7812 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2295 10.1970 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 7.8987 10.9402 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2514 10.4050 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8913 8.7108 0.0000 O 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 4 2 1 6 0 0 0 4 5 1 0 0 0 0 4 51 1 0 0 0 0 5 6 2 0 0 0 0 5 7 1 0 0 0 0 7 8 1 0 0 0 0 7 9 1 0 0 0 0 9 10 1 1 0 0 0 9 13 1 0 0 0 0 10 11 1 0 0 0 0 10 12 1 0 0 0 0 13 14 2 0 0 0 0 13 15 1 0 0 0 0 15 19 1 0 0 0 0 15 16 1 0 0 0 0 16 17 1 0 0 0 0 17 18 1 0 0 0 0 18 19 1 0 0 0 0 19 20 1 1 0 0 0 20 21 2 0 0 0 0 20 22 1 0 0 0 0 22 26 1 0 0 0 0 22 23 1 0 0 0 0 23 24 1 0 0 0 0 24 25 1 0 0 0 0 25 26 1 0 0 0 0 26 27 1 1 0 0 0 27 28 2 0 0 0 0 27 29 1 0 0 0 0 30 29 1 6 0 0 0 30 31 1 0 0 0 0 30 34 1 0 0 0 0 31 32 1 0 0 0 0 31 33 1 0 0 0 0 34 35 2 0 0 0 0 34 36 1 0 0 0 0 36 47 1 0 0 0 0 36 37 1 0 0 0 0 37 38 1 6 0 0 0 37 45 1 0 0 0 0 38 39 1 0 0 0 0 39 44 2 0 0 0 0 39 40 1 0 0 0 0 40 41 2 0 0 0 0 41 42 1 0 0 0 0 42 43 2 0 0 0 0 43 44 1 0 0 0 0 45 46 2 0 0 0 0 45 49 1 0 0 0 0 46 47 1 0 0 0 0 47 48 2 0 0 0 0 49 50 1 0 0 0 0 51 52 2 3 0 0 0 52 60 1 0 0 0 0 53 52 1 1 0 0 0 53 54 1 0 0 0 0 53 57 1 0 0 0 0 54 55 1 0 0 0 0 54 56 1 0 0 0 0 57 58 1 0 0 0 0 57 59 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	836.5
Volume:	868.742
LogP:	4.198
LogD:	3.283
LogS:	-4.567
# Rotatable Bonds:	23
TPSA:	171.03
# H-Bond Aceptor:	15
# H-Bond Donor:	2
# Rings:	4
# Heavy Atoms:	15

MedChem Properties

QED Drug-Likeness Score:	0.22
Synthetic Accessibility Score:	5.013
Fsp3:	0.644
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.392
MDCK Permeability:	1.0573100553301629e-05
Pgp-inhibitor:	0.954
Pgp-substrate:	0.968
Human Intestinal Absorption (HIA):	0.465
20% Bioavailability (F20%):	0.067
30% Bioavailability (F30%):	0.615

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.136
Plasma Protein Binding (PPB):	90.98799896240234%
Volume Distribution (VD):	0.764
Pgp-substrate:	5.4350433349609375%

ADMET: Metabolism

CYP1A2-inhibitor:	0.001
CYP1A2-substrate:	0.051
CYP2C19-inhibitor:	0.17
CYP2C19-substrate:	0.866
CYP2C9-inhibitor:	0.239
CYP2C9-substrate:	0.697
CYP2D6-inhibitor:	0.009
CYP2D6-substrate:	0.207
CYP3A4-inhibitor:	0.895
CYP3A4-substrate:	0.93

ADMET: Excretion

Clearance (CL):	10.741
Half-life (T1/2):	0.397

ADMET: Toxicity

hERG Blockers:	0.006
Human Hepatotoxicity (H-HT):	0.981
Drug-inuced Liver Injury (DILI):	0.989
AMES Toxicity:	0.015
Rat Oral Acute Toxicity:	0.337
Maximum Recommended Daily Dose:	0.231
Skin Sensitization:	0.029
Carcinogencity:	0.024
Eye Corrosion:	0.003
Eye Irritation:	0.003
Respiratory Toxicity:	0.156

Download Data

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

Natural Product: NPC489055

Natural Product ID:	NPC489055
*Common Name:**	LQKSHSFQQRCAFW-CCVNJFHASA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	LQKSHSFQQRCAFW-CCVNJFHASA-N
Standard InCHI:	InChI=1S/C45H68N6O9/c1-26(2)36(46-40(53)37(27(3)4)47(9)10)42(55)48(11)38(28(5)6)43(56)49-22-16-20-31(49)41(54)50-23-17-21-32(50)45(58)60-39(29(7)8)44(57)51-33(34(59-12)25-35(51)52)24-30-18-14-13-15-19-30/h13-15,18-19,25-29,31-33,36-39H,16-17,20-24H2,1-12H3,(H,46,53)/t31-,32-,33-,36-,37-,38-,39-/m0/s1
SMILES:	CC(C)[C@@H](C(=O)N(C)[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)O[C@@H](C(C)C)C(=O)N1[C@@H](Cc2ccccc2)C(=CC1=O)OC)N=C([C@H](C(C)C)N(C)C)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	9918978
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
ED50	1
IC50	13
Others	1

Activity Type	# Activity
Cell Line	9
CELL-LINE	2
Organism	1
Others	1
Protein Complex	1
Protein Family	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT168	Cell Line	P388	Mus musculus	ED50	=	2.4	ng ml-1	PMID[9871690]
NPT4850	Cell Line	Osteoclast-like		IC50	=	17.0	nM	DOI[10.1016/S0960-894X(01)80540-0]
NPT15	Cell Line	Jurkat	Homo sapiens	IC50	=	5.0	nM	DOI[10.1016/S0960-894X(01)80540-0]
NPT137	Cell Line	L1210	Mus musculus	IC50	=	0.15	nM	DOI[10.1016/S0960-894X(01)80540-0]
NPT2589	Cell Line	Panel leukemia (Carcinoma cell lines)	Homo sapiens	IC50	=	0.1	nM	DOI[10.1016/S0960-894X(01)80540-0]
NPT139	Cell Line	HT-29	Homo sapiens	IC50	=	0.29	nM	PMID[9554885]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	0.04	nM	PMID[9554885]
NPT137	Cell Line	L1210	Mus musculus	IC50	=	0.13	nM	PMID[9554885]
NPT397	Cell Line	NCI-H460	Homo sapiens	TC50	=	2.4	nM	PMID[19161344]
NPT26637	CELL-LINE	CTLL	Mus musculus	IC50	=	3.0	nM	DOI[10.1016/S0960-894X(01)80540-0]
NPT22801	CELL-LINE	Lymphoma cell line	n.a.	IC50	=	0.012	nM	DOI[10.1016/S0960-894X(01)80540-0]
NPT782	Protein Family	Tubulin	Bos taurus	IC50	=	17000.0	nM	PMID[9554885]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	200.0	nM	PMID[18334299]
NPT2	Others	Unspecified		IC50	=	23000.0	nM	PMID[23445405]
NPT518	Protein Complex	Tubulin	Homo sapiens	IC50	=	23000.0	nM	PMID[29431439]

☑ 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 NPC489055 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	152
0.1-0.2	835
0.2-0.3	3929
0.3-0.4	20686
0.4-0.5	13892
0.5-0.6	2415
0.6-0.7	512
0.7-0.8	217
0.8-0.85	49
0.85-0.9	9
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 NPC489055 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	109
0.1-0.2	370
0.2-0.3	715
0.3-0.4	2470
0.4-0.5	3986
0.5-0.6	1233
0.6-0.7	236
0.7-0.8	31
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