NPASS Compound

Structure

NPC478427 OpenBabel06302215572D 48 54 0 0 1 0 0 0 0 0999 V2000 -1.7321 -4.7321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -4.2321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -3.2321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -2.7321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -3.2321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -4.2321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -4.7321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -4.7321 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -2.7321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -3.2321 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -1.7321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -1.2321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -0.2321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 0.2679 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -0.2321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 0.2679 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.3301 -0.2321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 -1.2321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 -1.7321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 -1.2321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 -0.2321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 0.2679 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 1.2679 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 1.7679 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 1.7679 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 2.7679 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 3.2679 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 2.7679 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 3.2679 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 1.7679 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 1.2679 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 1.2679 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 3.2679 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9282 0.2679 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -1.2321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -1.7321 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -1.7321 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 -0.5000 -0.8660 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5000 -0.8660 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0000 -0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5000 0.8660 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.5000 0.8660 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0000 1.7321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0000 1.7321 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0000 -1.7321 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0000 -1.7321 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 2 7 2 0 0 0 0 2 3 1 0 0 0 0 3 4 2 0 0 0 0 4 37 1 0 0 0 0 4 5 1 0 0 0 0 5 6 2 0 0 0 0 5 9 1 0 0 0 0 6 7 1 0 0 0 0 6 8 1 0 0 0 0 9 10 2 0 0 0 0 9 11 1 0 0 0 0 11 35 2 0 0 0 0 11 12 1 0 0 0 0 12 13 2 0 0 0 0 12 37 1 0 0 0 0 13 14 1 0 0 0 0 14 15 2 0 0 0 0 15 35 1 0 0 0 0 16 15 1 6 0 0 0 16 17 1 0 0 0 0 16 31 1 0 0 0 0 17 22 2 0 0 0 0 17 18 1 0 0 0 0 18 19 2 0 0 0 0 19 20 1 0 0 0 0 20 21 2 0 0 0 0 21 22 1 0 0 0 0 21 34 1 0 0 0 0 22 23 1 0 0 0 0 23 24 2 0 0 0 0 23 25 1 0 0 0 0 25 31 2 0 0 0 0 25 26 1 0 0 0 0 26 27 2 0 0 0 0 26 33 1 0 0 0 0 27 28 1 0 0 0 0 28 29 1 0 0 0 0 28 30 2 0 0 0 0 30 31 1 0 0 0 0 30 32 1 0 0 0 0 35 36 1 0 0 0 0 37 38 1 0 0 0 0 37 48 1 0 0 0 0 38 39 1 0 0 0 0 38 44 1 1 0 0 0 39 40 1 0 0 0 0 39 47 1 6 0 0 0 40 41 1 0 0 0 0 40 46 1 6 0 0 0 41 42 1 0 0 0 0 41 45 1 1 0 0 0 42 43 1 6 0 0 0 42 44 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	656.19
Volume:	639.889
LogP:	5.758
LogD:	2.106
LogS:	-4.269
# Rotatable Bonds:	2
TPSA:	228.6
# H-Bond Aceptor:	12
# H-Bond Donor:	10
# Rings:	7
# Heavy Atoms:	12

MedChem Properties

QED Drug-Likeness Score:	0.098
Synthetic Accessibility Score:	4.899
Fsp3:	0.25
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-6.444
MDCK Permeability:	3.591350605347543e-06
Pgp-inhibitor:	0.146
Pgp-substrate:	0.162
Human Intestinal Absorption (HIA):	0.987
20% Bioavailability (F20%):	0.48
30% Bioavailability (F30%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001
Plasma Protein Binding (PPB):	98.43184661865234%
Volume Distribution (VD):	0.252
Pgp-substrate:	3.5807158946990967%

ADMET: Metabolism

CYP1A2-inhibitor:	0.367
CYP1A2-substrate:	0.189
CYP2C19-inhibitor:	0.043
CYP2C19-substrate:	0.051
CYP2C9-inhibitor:	0.645
CYP2C9-substrate:	0.146
CYP2D6-inhibitor:	0.013
CYP2D6-substrate:	0.129
CYP3A4-inhibitor:	0.045
CYP3A4-substrate:	0.068

ADMET: Excretion

Clearance (CL):	2.423
Half-life (T1/2):	0.113

ADMET: Toxicity

hERG Blockers:	0.02
Human Hepatotoxicity (H-HT):	0.195
Drug-inuced Liver Injury (DILI):	0.976
AMES Toxicity:	0.714
Rat Oral Acute Toxicity:	0.111
Maximum Recommended Daily Dose:	0.865
Skin Sensitization:	0.937
Carcinogencity:	0.11
Eye Corrosion:	0.003
Eye Irritation:	0.881
Respiratory Toxicity:	0.046

Download Data

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

Natural Product: NPC478427

Natural Product ID:	NPC478427
*Common Name:**	CALWHIFPEUURSN-GMHXHXQTSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	CALWHIFPEUURSN-GMHXHXQTSA-N
Standard InCHI:	InChI=1S/C36H32O12/c1-12-9-18-24(20(38)10-12)32(44)25-17(36(18,47)35-34(46)33(45)29(41)14(3)48-35)8-7-16(30(25)42)22-15-5-4-6-19(37)23(15)31(43)26-21(39)11-13(2)28(40)27(22)26/h4-11,14,22,29,33-35,37-42,45-47H,1-3H3/t14-,22+,29-,33+,34+,35+,36?/m0/s1
SMILES:	Cc1cc2c(c(c1)O)C(=O)c1c(ccc([C@H]3c4cccc(c4C(=O)c4c(cc(C)c(c34)O)O)O)c1O)C2([C@H]1[C@@H]([C@@H]([C@H]([C@H](C)O1)O)O)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	n.a.
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds]

*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
NPO40802	Bulbine natalensis	Species	n.a.	n.a.	Rhizomes	n.a.	n.a.	PMID[31287681]

☑ 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	6

Activity Type	# Activity
Organism	6

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20	Organism	Candida albicans	Candida albicans	IC50	>	30.0	nM	PMID[31287681]
NPT87	Organism	Aspergillus fumigatus	Aspergillus fumigatus	IC50	>	30.0	nM	PMID[31287681]
NPT85	Organism	Filobasidiella neoformans	Cryptococcus neoformans	IC50	>	30.0	nM	PMID[31287681]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IC50	=	20.0	nM	PMID[31287681]
NPT19	Organism	Escherichia coli	Escherichia coli	IC50	>	30.0	nM	PMID[31287681]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	IC50	>	30.0	nM	PMID[31287681]

☑ 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 NPC478427 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	384
0.1-0.2	1316
0.2-0.3	2882
0.3-0.4	7005
0.4-0.5	11094
0.5-0.6	6323
0.6-0.7	7226
0.7-0.8	6115
0.8-0.85	291
0.85-0.9	50
0.9-0.95	9
0.95-1	2

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 NPC478427 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	327
0.1-0.2	815
0.2-0.3	1529
0.3-0.4	2790
0.4-0.5	2207
0.5-0.6	1033
0.6-0.7	342
0.7-0.8	99
0.8-0.85	8
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