NPASS Compound

Structure

NPC145253 OpenBabel06302215422D 52 63 0 0 1 0 0 0 0 0999 V2000 1.6070 -0.2545 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8684 0.2821 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.8684 1.1952 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 1.4773 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5367 0.7387 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.4050 0.4565 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1957 0.9130 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9865 0.4565 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9865 -0.4565 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1957 -0.9130 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4050 -0.4565 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5367 -0.7387 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.1192 -1.8438 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0011 -1.6075 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6467 -2.2531 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4104 -3.1350 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5285 -3.3714 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8828 -2.7257 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0693 -3.1403 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.2121 -4.0421 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.1139 -4.1849 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.2568 -5.0867 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4432 -5.5012 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7976 -4.8556 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.8958 -4.9984 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0157 -4.3277 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5903 -3.6182 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4921 -3.7610 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8194 -4.6134 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2448 -5.3230 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3430 -5.1801 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9284 -5.9936 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.5741 -6.6393 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.3876 -6.2248 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.0332 -6.8704 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6187 -7.6839 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7169 -7.5411 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.0713 -8.1867 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6417 -4.5667 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.5101 -4.2846 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5101 -3.3715 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6417 -3.0894 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -8.3596 -2.2210 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1050 -3.8280 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.2367 -4.1102 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -7.2367 -5.0232 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5581 -5.6342 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7480 -6.5273 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6163 -6.8094 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2949 -6.1985 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1050 -5.3054 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 2 13 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 13 1 0 0 0 0 5 6 1 0 0 0 0 5 14 1 6 0 0 0 6 11 2 0 0 0 0 6 7 1 0 0 0 0 7 8 2 0 0 0 0 8 9 1 0 0 0 0 9 10 2 0 0 0 0 10 11 1 0 0 0 0 11 12 1 0 0 0 0 13 12 1 1 0 0 0 14 19 2 0 0 0 0 14 15 1 0 0 0 0 15 16 2 0 0 0 0 16 17 1 0 0 0 0 17 18 2 0 0 0 0 18 22 1 0 0 0 0 18 19 1 0 0 0 0 19 20 1 0 0 0 0 21 20 1 6 0 0 0 21 22 1 0 0 0 0 21 25 1 0 0 0 0 22 23 1 0 0 0 0 22 27 1 1 0 0 0 23 24 1 0 0 0 0 24 25 1 0 0 0 0 25 26 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 30 31 2 0 0 0 0 31 35 1 0 0 0 0 31 32 1 0 0 0 0 32 33 1 0 0 0 0 34 33 1 6 0 0 0 34 35 1 0 0 0 0 34 38 1 0 0 0 0 35 36 1 6 0 0 0 35 40 1 0 0 0 0 36 37 1 0 0 0 0 37 38 1 0 0 0 0 38 39 1 0 0 0 0 40 52 1 0 0 0 0 40 41 1 1 0 0 0 40 45 1 0 0 0 0 41 42 1 0 0 0 0 42 43 1 0 0 0 0 43 44 1 0 0 0 0 43 45 1 0 0 0 0 45 46 1 6 0 0 0 46 47 1 0 0 0 0 47 52 2 0 0 0 0 47 48 1 0 0 0 0 48 49 2 0 0 0 0 49 50 1 0 0 0 0 50 51 2 0 0 0 0 51 52 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	690.42
Volume:	723.239
LogP:	4.418
LogD:	3.134
LogS:	-4.212
# Rotatable Bonds:	3
TPSA:	61.08
# H-Bond Aceptor:	8
# H-Bond Donor:	4
# Rings:	12
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.216
Synthetic Accessibility Score:	5.48
Fsp3:	0.455
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
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:	-5.72
MDCK Permeability:	4.829506451642374e-06
Pgp-inhibitor:	0.745
Pgp-substrate:	0.998
Human Intestinal Absorption (HIA):	0.983
20% Bioavailability (F20%):	0.996
30% Bioavailability (F30%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.83
Plasma Protein Binding (PPB):	87.3189468383789%
Volume Distribution (VD):	2.669
Pgp-substrate:	11.341251373291016%

ADMET: Metabolism

CYP1A2-inhibitor:	0.005
CYP1A2-substrate:	0.109
CYP2C19-inhibitor:	0.231
CYP2C19-substrate:	0.993
CYP2C9-inhibitor:	0.019
CYP2C9-substrate:	0.051
CYP2D6-inhibitor:	0.944
CYP2D6-substrate:	0.935
CYP3A4-inhibitor:	0.161
CYP3A4-substrate:	0.919

ADMET: Excretion

Clearance (CL):	6.349
Half-life (T1/2):	0.022

ADMET: Toxicity

hERG Blockers:	0.604
Human Hepatotoxicity (H-HT):	0.285
Drug-inuced Liver Injury (DILI):	0.006
AMES Toxicity:	0.545
Rat Oral Acute Toxicity:	0.741
Maximum Recommended Daily Dose:	0.986
Skin Sensitization:	0.824
Carcinogencity:	0.071
Eye Corrosion:	0.003
Eye Irritation:	0.004
Respiratory Toxicity:	0.497

Download Data

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

Natural Product: NPC145253

Natural Product ID:	NPC145253
*Common Name:**	AVQUGAAZHJLAOQ-YQNMZVCZSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	AVQUGAAZHJLAOQ-YQNMZVCZSA-N
Standard InCHI:	InChI=1S/C44H50N8/c1-49-23-19-41(27-11-5-7-17-33(27)45-37(41)49)29-13-9-14-30-35(29)47-38-42(30,20-24-50(38)2)31-15-10-16-32-36(31)48-40-44(32,22-26-52(40)4)43-21-25-51(3)39(43)46-34-18-8-6-12-28(34)43/h5-18,37-40,45-48H,19-26H2,1-4H3/t37-,38-,39+,40-,41-,42-,43-,44+/m1/s1
SMILES:	CN1CC[C@@]2(c3ccccc3N[C@H]12)c1cccc2c1N[C@H]1[C@@]2(CCN1C)c1cccc2c1N[C@H]1[C@@]2(CCN1C)[C@]12CCN(C)[C@@H]2Nc2ccccc12
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	10604660
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000211] Indoles and derivatives [CHEMONTID:0001733] Pyrroloindoles

*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
NPO6968	Psychotria rostrata	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6968	Psychotria rostrata	Species	Rubiaceae	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 NPC145253 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	916
0.1-0.2	6913
0.2-0.3	21719
0.3-0.4	8520
0.4-0.5	3598
0.5-0.6	945
0.6-0.7	73
0.7-0.8	11
0.8-0.85	1
0.85-0.9	0
0.9-0.95	1
0.95-1	0

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 NPC145253 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	386
0.1-0.2	719
0.2-0.3	1355
0.3-0.4	2657
0.4-0.5	3065
0.5-0.6	911
0.6-0.7	55
0.7-0.8	2
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