NPASS Compound

Natural Product: NPC483624

Natural Product ID	NPC483624
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	NUUWMADFOQFENP-PDBXOOCHSA-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 67 67 0 0 0 0 0 0 0 0999 V2000 8.7690 1.2054 0.0363 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6683 -0.2063 0.6502 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6144 -1.2278 -0.3608 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6798 -2.0975 -0.5637 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4461 -2.2886 0.1615 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0937 -1.5331 1.3297 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0574 -0.7121 1.3655 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1388 -0.4609 0.2302 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7580 -0.8306 0.5440 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7334 0.0271 0.5413 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9114 1.4219 0.2240 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3164 2.0662 -0.9488 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1366 2.1391 -1.1836 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7986 0.8497 -1.4245 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2973 0.9940 -1.6795 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0420 1.6131 -0.5571 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9564 0.8876 0.7558 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4868 -0.4826 0.6838 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5246 -0.8805 1.3334 N 0 0 0 0 0 0 0 0 0 0 0 0 -5.3294 -0.0921 2.2171 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3539 0.7328 1.4473 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2493 -0.1617 0.6759 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3888 -0.6047 1.2925 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2382 -1.4439 0.5815 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.9301 -1.8088 -0.7005 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7756 -1.3467 -1.2947 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9301 -0.5199 -0.6065 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8552 -1.4251 -0.1207 O 0 0 0 0 0 0 0 0 0 0 0 0 8.4910 1.9648 0.7957 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1361 1.2924 -0.8574 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8131 1.4243 -0.2679 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6896 -0.3157 1.1604 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9612 -0.1293 1.4383 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5158 -1.2661 -1.0672 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8308 -2.8355 -1.4420 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5623 -2.4631 -0.5402 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5172 -3.4011 0.5792 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6364 -1.6213 2.2984 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8247 -0.1495 2.2997 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2711 0.5949 -0.1123 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4154 -1.0469 -0.6956 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5452 -1.8548 0.7932 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7418 -0.3800 0.8468 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9605 1.8040 0.4326 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3710 1.9668 1.1312 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8433 1.5856 -1.8560 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7848 3.1186 -1.0041 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5885 2.5645 -0.2277 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3247 2.8882 -2.0121 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5836 0.0981 -0.7011 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4032 0.4594 -2.4181 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4481 1.5570 -2.6500 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6820 -0.0123 -1.8890 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8233 2.6930 -0.4137 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1315 1.5874 -0.8429 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8747 0.8107 1.0702 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4432 1.4583 1.5753 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7073 0.5460 2.8667 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8657 -0.7906 2.9217 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9475 1.2778 2.2335 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8360 1.4839 0.8323 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6103 -0.3034 2.3038 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1187 -1.7710 1.0926 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5904 -2.4531 -1.2346 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5865 -1.6691 -2.3079 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0359 -0.1708 -1.0879 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2038 -2.3561 -0.1582 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 3 19 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 18 28 1 0 27 22 1 0 1 29 1 0 1 30 1 0 1 31 1 0 2 32 1 0 2 33 1 0 3 34 1 0 4 35 1 0 5 36 1 0 5 37 1 0 6 38 1 0 7 39 1 0 8 40 1 0 8 41 1 0 9 42 1 0 10 43 1 0 11 44 1 0 11 45 1 0 12 46 1 0 12 47 1 0 13 48 1 0 13 49 1 0 14 50 1 0 14 51 1 0 15 52 1 0 15 53 1 0 16 54 1 0 16 55 1 0 17 56 1 0 17 57 1 0 20 58 1 0 20 59 1 0 21 60 1 0 21 61 1 0 23 62 1 0 24 63 1 0 25 64 1 0 26 65 1 0 27 66 1 0 28 67 1 0 M END

Standard InCHIKey	NUUWMADFOQFENP-PDBXOOCHSA-N
Standard InCHI	InChI=1S/C26H39NO/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-19-22-26(28)27-24-23-25-20-17-16-18-21-25/h3-4,6-7,9-10,16-18,20-21H,2,5,8,11-15,19,22-24H2,1H3,(H,27,28)/b4-3-,7-6-,10-9-
SMILES	CC/C=CC/C=CC/C=CCCCCCCCC(=NCCc1ccccc1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	381.3	Volume:	451.027 ? Van der Waals volume.
Dense:	0.845	LogP:	7.072 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.095 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-6.648 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	16.0	Rigid Bonds:	10.0
TPSA:	32.59 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	1.0	Rings:	1.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.135	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.811	Fsp³:	0.5
MCE-18:	5.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.695	Fluc inhibitor:	0.125 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.007 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.464 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.346	Promiscuous compounds:	0.11

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.991	MDCK Permeability:	-4.76
Pgp-inhibitor:	0.853	Pgp-substrate:	0.016
PAMPA:	0.0 ? 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):	0.018
20% Bioavailability (F20%):	0.636	30% Bioavailability (F30%):	0.867
50% Bioavailability (F50%):	0.978

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.107	MRP1:	0.975
Plasma Protein Binding (PPB):	98.727%	Volume Distribution (VD):	0.225
Fu:	0.703% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.014
OATP1B3 inhibitor:	0.121	BCRP inhibitor:	0.512
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.938
CYP2C19-inhibitor:	0.283	CYP2C19-substrate:	0.047
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.002
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.923
CYP3A4-inhibitor:	0.012	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.995	CYP2C8-inhibitor:	1.0
HLM stability:	0.009 ? 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):

6.523

Half-life (T1/2):

0.171

ADMET: Toxicity

hERG Blockers:	0.587	hERG Blockers (10um):	0.77
Human Hepatotoxicity (H-HT):	0.113	Drug-induced Liver Injury (DILI):	0.0
AMES Toxicity:	0.867	Rat Oral Acute Toxicity:	0.076
Maximum Recommended Daily Dose:	0.001	Skin Sensitization:	1.0
Carcinogencity:	0.004	Eye Corrosion:	1.0
Eye Irritation:	1.0	Respiratory Toxicity:	0.992
Drug-induced Neurotoxicity:	0.026	Ototoxicity:	0.077
Hematotoxicity:	0.0	Drug-induced Nephrotoxicity:	0.767
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.005
A549 Cytotoxicity:	0.107	Hek293 Cytotoxicity:	0.003
BCF:	1.629 ? 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:	4.729 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.03 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.053 ? 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
NPO18988	Lepidium meyenii	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12932133]
NPO18988	Lepidium meyenii	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23891163]
NPO18988	Lepidium meyenii	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24972328]
NPO18988	Lepidium meyenii	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[33320645]
NPO18988	Lepidium meyenii	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18988	Lepidium meyenii	Species	Brassicaceae	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	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
IC50	3

Activity Type	# Activity
Individual protein	2
Single protein	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT862	Individual protein	Epoxide hydratase	Homo sapiens	IC50	=	15.0	nM	PMID[33320645]
NPT21303	Single protein	Epoxide hydratase	Mus musculus	IC50	=	39.0	nM	PMID[33320645]
NPT5882	Individual protein	Epoxide hydrolase 2	Rattus norvegicus	IC50	=	15.0	nM	PMID[33320645]

In vitro activity

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

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 NPC483624 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	27371
0.1-0.2	20958
0.2-0.3	1362
0.3-0.4	135
0.4-0.5	17
0.5-0.6	6
0.6-0.7	6
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.913	High Similarity	NPC483623
0.6981	Remote Similarity	NPC231705
0.6863	Remote Similarity	NPC489840
0.6226	Remote Similarity	NPC486087
0.6111	Remote Similarity	NPC486088
0.6038	Remote Similarity	NPC121872
0.6034	Remote Similarity	NPC58674
0.5741	Remote Similarity	NPC489324
0.5593	Remote Similarity	NPC12429
0.5455	Remote Similarity	NPC209764
0.537	Remote Similarity	NPC258056
0.537	Remote Similarity	NPC483617
0.5147	Remote Similarity	NPC469763

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC483624 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3077
0.1-0.2	5648
0.2-0.3	409
0.3-0.4	14
0.4-0.5	1
0.5-0.6	1
0.6-0.7	0
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
0.5556	Remote Similarity	NPD6690	Phase 2

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