NPASS Compound

Natural Product: NPC485937

Natural Product ID	NPC485937
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	VGDQBNXQAOYMPS-ZKJYXZACSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 52 56 0 0 0 0 0 0 0 0999 V2000 -1.1541 -2.6017 1.4697 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2902 -1.6010 1.3775 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2690 -0.8978 0.0486 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.3994 0.1228 -0.0875 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5589 1.2684 -0.7407 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5891 1.5127 0.4478 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4189 0.8979 0.0481 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7791 0.4342 0.7482 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6655 -0.3209 -0.0724 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5379 -0.7258 -1.4972 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3481 -0.3250 -2.2823 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9290 -0.2460 -1.8269 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.9875 0.6157 -1.9903 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9560 -0.4393 -0.4280 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7232 -0.6485 0.7349 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8695 -1.3506 0.5279 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7541 -1.5069 1.5724 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5080 -0.9703 2.8224 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3408 -0.2624 3.0113 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4421 -0.0985 1.9657 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2541 0.5567 1.9547 N 0 0 0 0 0 0 0 0 0 0 0 0 0.1678 1.8924 -0.9020 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4093 2.0121 -1.1099 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5142 2.8051 -1.6646 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0096 3.7407 -2.5440 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4697 -2.3703 1.5235 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1834 -2.1388 1.6772 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1203 -3.1239 0.4697 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4369 -3.3834 2.2127 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1790 -0.9358 2.2560 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5666 -1.7108 -0.6887 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7130 0.4467 0.9265 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2065 -0.1833 -0.7434 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1783 2.1210 -0.9575 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5446 2.6494 0.4899 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0704 1.2915 1.4231 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4422 -0.3472 -2.0217 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7217 -1.8453 -1.4613 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5487 0.4415 -3.1020 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2852 -1.2228 -3.0218 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8425 -0.1266 -2.2686 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0942 1.2190 -2.9235 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2676 -1.3170 -0.2518 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0396 -1.7608 -0.4589 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6582 -2.0553 1.4263 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2292 -1.1079 3.6423 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1288 0.1694 3.9928 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7498 1.0757 2.7030 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0826 4.7554 -2.0575 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0981 3.5775 -2.6695 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4943 3.7805 -3.5316 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1754 -1.7622 1.8315 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 12 14 1 0 9 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 7 22 1 6 22 23 2 0 22 24 1 0 24 25 1 0 2 26 1 0 14 3 1 0 20 15 1 0 13 5 1 0 14 7 1 0 21 8 1 0 1 27 1 0 1 28 1 0 1 29 1 0 2 30 1 1 3 31 1 6 4 32 1 0 4 33 1 0 5 34 1 6 6 35 1 0 6 36 1 0 10 37 1 0 10 38 1 0 11 39 1 0 11 40 1 0 13 41 1 0 13 42 1 0 14 43 1 0 16 44 1 0 17 45 1 0 18 46 1 0 19 47 1 0 21 48 1 0 25 49 1 0 25 50 1 0 25 51 1 0 26 52 1 0 M END

Standard InCHIKey	VGDQBNXQAOYMPS-ZKJYXZACSA-N
Standard InCHI	InChI=1S/C21H26N2O3/c1-12(24)16-9-13-10-21(20(25)26-2)18-15(7-8-23(11-13)19(16)21)14-5-3-4-6-17(14)22-18/h3-6,12-13,16,19,22,24H,7-11H2,1-2H3/t12-,13-,16+,19?,21+/m0/s1
SMILES	C[C@@H]([C@H]1C[C@H]2C[C@]3(c4c(CCN(C2)C13)c1ccccc1[nH]4)C(=O)OC)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	354.19	Volume:	364.172 ? Van der Waals volume.
Dense:	0.973	LogP:	2.574 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.691 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.62 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	24.0
TPSA:	65.56 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	6.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.812	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.181	Fsp³:	0.571
MCE-18:	99.273 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.137	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.567 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.114 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.145

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.88	MDCK Permeability:	-5.196
Pgp-inhibitor:	0.003	Pgp-substrate:	0.723
PAMPA:	0.506 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.0
20% Bioavailability (F20%):	0.022	30% Bioavailability (F30%):	0.079
50% Bioavailability (F50%):	0.622

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.3	MRP1:	0.978
Plasma Protein Binding (PPB):	58.261%	Volume Distribution (VD):	0.111
Fu:	41.804% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.238
OATP1B3 inhibitor:	0.416	BCRP inhibitor:	0.725
BSEP inhibitor:	0.97

ADMET: Metabolism

CYP1A2-inhibitor:	0.978	CYP1A2-substrate:	0.011
CYP2C19-inhibitor:	0.984	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.896
CYP2D6-inhibitor:	0.449	CYP2D6-substrate:	0.971
CYP3A4-inhibitor:	0.967	CYP3A4-substrate:	0.002
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.933
HLM stability:	0.993 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

8.822

Half-life (T1/2):

1.903

ADMET: Toxicity

hERG Blockers:	0.162	hERG Blockers (10um):	0.353
Human Hepatotoxicity (H-HT):	0.689	Drug-induced Liver Injury (DILI):	0.491
AMES Toxicity:	0.777	Rat Oral Acute Toxicity:	0.643
Maximum Recommended Daily Dose:	0.879	Skin Sensitization:	0.924
Carcinogencity:	0.602	Eye Corrosion:	0.0
Eye Irritation:	0.327	Respiratory Toxicity:	0.967
Drug-induced Neurotoxicity:	0.509	Ototoxicity:	0.796
Hematotoxicity:	0.428	Drug-induced Nephrotoxicity:	0.834
Genotoxicity:	0.925	RPMI-8226 Immunitoxicity:	0.095
A549 Cytotoxicity:	0.507	Hek293 Cytotoxicity:	0.713
BCF:	0.584 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	3.302 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.915 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.189 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18778099]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	leaf	n.a.	PMID[18778099]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	Leaves	n.a.	n.a.	PMID[24773071]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	stem-bark	Pahang, Malaysia	2003-JUN	PMID[25919190]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26918761]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27077800]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29319316]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30869890]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32356659]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]

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	Organism Name	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
EC50	1

Activity Type	# Activity
Cell line	1

Molecular-level activity

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

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT165	Cell line	HeLa	Homo sapiens	EC50	>	40000.0	nM	PMID[32356659]

In vivo activity

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

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

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 toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC485937 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	14785
0.1-0.2	33630
0.2-0.3	1090
0.3-0.4	249
0.4-0.5	62
0.5-0.6	22
0.6-0.7	9
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC485936
0.8406	Intermediate Similarity	NPC329858
0.8169	Intermediate Similarity	NPC482061
0.7838	Intermediate Similarity	NPC473105
0.7733	Intermediate Similarity	NPC474192
0.6582	Remote Similarity	NPC469928
0.6582	Remote Similarity	NPC330009
0.6538	Remote Similarity	NPC473041
0.6465	Remote Similarity	NPC485966
0.6456	Remote Similarity	NPC96321
0.6456	Remote Similarity	NPC111993
0.6456	Remote Similarity	NPC485938
0.6375	Remote Similarity	NPC314333
0.6375	Remote Similarity	NPC606568
0.5979	Remote Similarity	NPC485963
0.5974	Remote Similarity	NPC189812
0.5974	Remote Similarity	NPC329688
0.5795	Remote Similarity	NPC485947
0.5686	Remote Similarity	NPC17437
0.5631	Remote Similarity	NPC485933
0.5631	Remote Similarity	NPC485970
0.5618	Remote Similarity	NPC485946
0.5607	Remote Similarity	NPC485913
0.5588	Remote Similarity	NPC485969
0.5577	Remote Similarity	NPC475666
0.5529	Remote Similarity	NPC485887
0.5429	Remote Similarity	NPC81939
0.5357	Remote Similarity	NPC488883
0.5321	Remote Similarity	NPC485960
0.5315	Remote Similarity	NPC488882
0.5315	Remote Similarity	NPC485918
0.5315	Remote Similarity	NPC485915
0.5268	Remote Similarity	NPC605382
0.5229	Remote Similarity	NPC485922
0.5172	Remote Similarity	NPC187106
0.5114	Remote Similarity	NPC485941

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC485937 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3351
0.1-0.2	5574
0.2-0.3	206
0.3-0.4	13
0.4-0.5	4
0.5-0.6	1
0.6-0.7	1
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
0.6375	Remote Similarity	NPD4499	Approved
0.537	Remote Similarity	NPD8358	Approved

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by 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