NPASS Compound

Structure

NPC111488 OpenBabel06302215322D 47 53 0 0 1 0 0 0 0 0999 V2000 3.4641 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -1.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -0.5000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.1530 -0.7254 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7511 -0.7584 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8611 -1.7523 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7495 -1.7929 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2288 -1.0438 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8197 -0.2541 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3275 -0.5954 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1745 0.2285 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3533 0.8002 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3368 1.3990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1267 1.9599 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7460 2.4223 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6002 2.2798 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9038 1.4687 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2357 2.7360 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6512 2.8670 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6790 3.3223 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.3404 3.6281 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8902 3.5539 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6675 3.1557 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1482 3.0732 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8888 2.6158 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0848 2.1278 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5141 2.5454 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0558 2.8011 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8143 1.5933 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 1.0000 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 -0.8660 -0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 2.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8911 2.6826 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4501 3.5802 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2278 -1.0893 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6878 -1.9772 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 2 7 1 0 0 0 0 2 3 1 0 0 0 0 3 4 1 0 0 0 0 4 5 1 0 0 0 0 5 37 2 0 0 0 0 5 6 1 0 0 0 0 6 34 2 0 0 0 0 6 7 1 0 0 0 0 7 8 1 6 0 0 0 8 9 1 0 0 0 0 9 14 2 0 0 0 0 9 10 1 0 0 0 0 10 11 2 0 0 0 0 11 12 1 0 0 0 0 12 13 2 0 0 0 0 12 46 1 0 0 0 0 13 14 1 0 0 0 0 13 15 1 0 0 0 0 15 16 1 0 0 0 0 16 21 2 0 0 0 0 16 17 1 0 0 0 0 17 18 2 0 0 0 0 18 19 1 0 0 0 0 19 20 2 0 0 0 0 19 22 1 0 0 0 0 20 21 1 0 0 0 0 22 23 1 0 0 0 0 23 32 1 0 0 0 0 23 24 2 0 0 0 0 24 25 1 0 0 0 0 25 26 1 0 0 0 0 26 27 1 0 0 0 0 27 32 2 0 0 0 0 27 28 1 0 0 0 0 28 29 2 0 0 0 0 29 30 1 0 0 0 0 29 44 1 0 0 0 0 30 31 2 0 0 0 0 30 33 1 0 0 0 0 31 32 1 0 0 0 0 33 34 1 0 0 0 0 34 35 1 0 0 0 0 35 36 2 0 0 0 0 35 42 1 0 0 0 0 36 37 1 0 0 0 0 36 40 1 0 0 0 0 37 38 1 0 0 0 0 38 39 1 0 0 0 0 40 41 1 0 0 0 0 42 43 1 0 0 0 0 44 45 1 0 0 0 0 46 47 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	636.28
Volume:	655.16
LogP:	6.401
LogD:	3.878
LogS:	-6.807
# Rotatable Bonds:	5
TPSA:	80.21
# H-Bond Aceptor:	9
# H-Bond Donor:	0
# Rings:	8
# Heavy Atoms:	9

MedChem Properties

QED Drug-Likeness Score:	0.232
Synthetic Accessibility Score:	5.694
Fsp3:	0.342
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:	-5.727
MDCK Permeability:	2.790288817777764e-05
Pgp-inhibitor:	0.998
Pgp-substrate:	0.977
Human Intestinal Absorption (HIA):	0.009
20% Bioavailability (F20%):	0.052
30% Bioavailability (F30%):	0.676

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.065
Plasma Protein Binding (PPB):	70.58051300048828%
Volume Distribution (VD):	0.591
Pgp-substrate:	11.94122314453125%

ADMET: Metabolism

CYP1A2-inhibitor:	0.047
CYP1A2-substrate:	0.969
CYP2C19-inhibitor:	0.13
CYP2C19-substrate:	0.962
CYP2C9-inhibitor:	0.092
CYP2C9-substrate:	0.854
CYP2D6-inhibitor:	0.001
CYP2D6-substrate:	0.936
CYP3A4-inhibitor:	0.17
CYP3A4-substrate:	0.957

ADMET: Excretion

Clearance (CL):	8.871
Half-life (T1/2):	0.132

ADMET: Toxicity

hERG Blockers:	0.968
Human Hepatotoxicity (H-HT):	0.041
Drug-inuced Liver Injury (DILI):	0.822
AMES Toxicity:	0.061
Rat Oral Acute Toxicity:	0.788
Maximum Recommended Daily Dose:	0.987
Skin Sensitization:	0.626
Carcinogencity:	0.03
Eye Corrosion:	0.003
Eye Irritation:	0.005
Respiratory Toxicity:	0.69

Download Data

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

Natural Product: NPC111488

Natural Product ID:	NPC111488
*Common Name:**	YWNUNVSMOKMJMG-LJAQVGFWSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	YWNUNVSMOKMJMG-LJAQVGFWSA-N
Standard InCHI:	InChI=1S/C38H40N2O7/c1-40-16-14-26-34-29(40)18-23-9-12-30(41-2)32(19-23)46-25-10-7-22(8-11-25)17-28-27-21-33(31(42-3)20-24(27)13-15-39-28)47-36(34)38(45-6)37(44-5)35(26)43-4/h7-12,19-21,29H,13-18H2,1-6H3/t29-/m0/s1
SMILES:	CN1CCc2c3[C@@H]1Cc1ccc(c(c1)Oc1ccc(cc1)CC1=NCCc4cc(c(cc14)Oc3c(c(c2OC)OC)OC)OC)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	362568
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000238] Tannins

*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
NPO20891	Coleonema pulchellum	Species	Rutaceae	Eukaryota	n.a.	Costa Rica; Bartica, Guyana	n.a.	PMID[16124770]
NPO13637	Thalictrum foliolosum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22494	Thalictrum rugosum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22044	Tamarix chinensis	Species	Tamaricaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO20891	Coleonema pulchellum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22494	Thalictrum rugosum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13637	Thalictrum foliolosum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22044	Tamarix chinensis	Species	Tamaricaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22044	Tamarix chinensis	Species	Tamaricaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO13637	Thalictrum foliolosum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO22494	Thalictrum rugosum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO22044	Tamarix chinensis	Species	Tamaricaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO22494	Thalictrum rugosum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13637	Thalictrum foliolosum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20320	Cryptostegia madagascariensis	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21985	Koenigia coriaria	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20451	Vitex scabra	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20891	Coleonema pulchellum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22625	Copris tripartitus	Species	Scarabaeidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22044	Tamarix chinensis	Species	Tamaricaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

☑ 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

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

☑ 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 NPC111488 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	472
0.1-0.2	2198
0.2-0.3	11345
0.3-0.4	6518
0.4-0.5	7417
0.5-0.6	11077
0.6-0.7	3062
0.7-0.8	473
0.8-0.85	43
0.85-0.9	62
0.9-0.95	26
0.95-1	4

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 NPC111488 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	233
0.1-0.2	776
0.2-0.3	1081
0.3-0.4	2051
0.4-0.5	2726
0.5-0.6	1690
0.6-0.7	527
0.7-0.8	57
0.8-0.85	3
0.85-0.9	2
0.9-0.95	4
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