NPASS Compound

Natural Product: NPC234897

Natural Product ID	NPC234897
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	NIKHGUQULKYIGE-SLBIIXIFSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	92529179
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0003782] Kaurane diterpenoids

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 55 0 0 0 0 0 0 0 0999 V2000 -4.7849 1.2631 1.1007 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6589 1.0173 0.4680 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3270 1.5766 0.7284 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3869 0.9070 -0.2976 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3539 1.9219 -0.6185 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8920 1.6094 0.2030 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4149 0.3061 -0.4221 C 0 0 2 0 0 0 0 0 0 0 0 0 0.4737 -0.8246 -0.1698 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3612 -1.6471 -1.4111 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9385 -1.7673 0.9427 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3735 -2.0853 0.9068 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1685 -1.3563 -0.1261 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8333 0.1046 -0.0421 C 0 0 2 0 0 0 0 0 0 0 0 0 3.1701 0.6448 1.3314 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7183 0.8279 -0.9902 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5497 0.1886 -1.6533 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6552 2.2040 -1.1689 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8894 -0.3330 0.3439 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8374 -1.4722 0.3972 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2031 -1.2680 -0.1264 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5200 0.0834 -0.6820 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3597 0.7060 -1.4185 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7010 0.7745 0.7984 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8671 1.9479 1.9380 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2976 2.6632 0.6418 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9687 1.3093 1.7610 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0514 1.8507 -1.6843 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6634 2.9573 -0.3618 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6325 2.3895 -0.0391 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6876 1.5037 1.2659 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4004 0.5321 -1.5312 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6253 -1.7274 -1.8520 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7319 -2.7043 -1.2758 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0274 -1.2465 -2.2331 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6061 -1.3629 1.9432 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3586 -2.7039 0.8070 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8185 -1.8383 1.9065 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5880 -3.1845 0.7668 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0999 -1.7478 -1.1377 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2565 -1.4429 0.1653 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3558 0.5747 2.0483 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1024 0.1619 1.6910 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4054 1.7438 1.2227 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5124 2.7345 -1.3321 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6566 -0.0330 1.4131 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9385 -1.8469 1.4640 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4291 -2.4008 -0.1128 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4701 -2.0065 -0.9403 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9896 -1.4719 0.6593 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4378 0.0628 -1.2746 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0108 0.1755 -2.2832 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7043 1.7290 -1.7300 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 4 3 1 1 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 6 8 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 1 13 15 1 0 15 16 2 0 15 17 1 0 8 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 21 2 1 0 22 4 1 0 18 4 1 0 13 7 1 0 1 23 1 0 1 24 1 0 3 25 1 0 3 26 1 0 5 27 1 0 5 28 1 0 6 29 1 0 6 30 1 0 7 31 1 6 9 32 1 0 9 33 1 0 9 34 1 0 10 35 1 0 10 36 1 0 11 37 1 0 11 38 1 0 12 39 1 0 12 40 1 0 14 41 1 0 14 42 1 0 14 43 1 0 17 44 1 0 18 45 1 1 19 46 1 0 19 47 1 0 20 48 1 0 20 49 1 0 21 50 1 6 22 51 1 0 22 52 1 0 M END

Standard InCHIKey	NIKHGUQULKYIGE-SLBIIXIFSA-N
Standard InCHI	InChI=1S/C20H30O2/c1-13-11-20-10-7-15-18(2,16(20)6-5-14(13)12-20)8-4-9-19(15,3)17(21)22/h14-16H,1,4-12H2,2-3H3,(H,21,22)/t14-,15-,16+,18-,19-,20-/m1/s1
SMILES	C=C1C[C@]23CC[C@@H]4[C@@](C)(CCC[C@@]4(C)C(=O)O)[C@@H]3CC[C@@H]1C2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	302.22	Volume:	332.558 ? Van der Waals volume.
Dense:	0.909	LogP:	2.949 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.623 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.611 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	21.0
TPSA:	37.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.689	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.468	Fsp³:	0.85
MCE-18:	99.081 ? 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:	0.368	Fluc inhibitor:	0.011 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.011 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.836	Promiscuous compounds:	0.049

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.171	MDCK Permeability:	-5.014
Pgp-inhibitor:	0.029	Pgp-substrate:	0.277
PAMPA:	0.962 ? 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%):	0.028	30% Bioavailability (F30%):	0.009
50% Bioavailability (F50%):	0.022

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.067	MRP1:	0.935
Plasma Protein Binding (PPB):	98.611%	Volume Distribution (VD):	-0.268
Fu:	1.664% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.946
OATP1B3 inhibitor:	0.05	BCRP inhibitor:	0.074
BSEP inhibitor:	0.952

ADMET: Metabolism

CYP1A2-inhibitor:	0.584	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.229	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.433	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.847	CYP3A4-substrate:	0.02
CYP2B6-substrate:	0.001	CYP2C8-inhibitor:	0.0
HLM stability:	0.001 ? 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):

2.423

Half-life (T1/2):

1.151

ADMET: Toxicity

hERG Blockers:	0.018	hERG Blockers (10um):	0.03
Human Hepatotoxicity (H-HT):	0.623	Drug-induced Liver Injury (DILI):	0.571
AMES Toxicity:	0.313	Rat Oral Acute Toxicity:	0.331
Maximum Recommended Daily Dose:	0.263	Skin Sensitization:	0.962
Carcinogencity:	0.738	Eye Corrosion:	0.865
Eye Irritation:	0.959	Respiratory Toxicity:	0.852
Drug-induced Neurotoxicity:	0.03	Ototoxicity:	0.48
Hematotoxicity:	0.618	Drug-induced Nephrotoxicity:	0.943
Genotoxicity:	0.341	RPMI-8226 Immunitoxicity:	0.029
A549 Cytotoxicity:	0.062	Hek293 Cytotoxicity:	0.038
BCF:	1.544 ? 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:	4.116 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.432 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.881 ? 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
NPO21765	Isodon henryi	Species	Lamiaceae	Eukaryota	n.a.	leaf	n.a.	PMID[19031362]
NPO17906	Anopterus macleayanus	Species	Escalloniaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26600001]
NPO21765	Isodon henryi	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17906	Anopterus macleayanus	Species	Escalloniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21765	Isodon henryi	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO17906	Anopterus macleayanus	Species	Escalloniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21765	Isodon henryi	Species	Lamiaceae	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

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

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 NPC234897 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	30858
0.1-0.2	17019
0.2-0.3	1714
0.3-0.4	139
0.4-0.5	80
0.5-0.6	27
0.6-0.7	7
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC330659
1.0	High Similarity	NPC244708
1.0	High Similarity	NPC161187
0.6275	Remote Similarity	NPC268736
0.6275	Remote Similarity	NPC477931
0.6154	Remote Similarity	NPC170985
0.6111	Remote Similarity	NPC607026
0.6071	Remote Similarity	NPC471037
0.6038	Remote Similarity	NPC212661
0.6038	Remote Similarity	NPC471035
0.5962	Remote Similarity	NPC252032
0.5962	Remote Similarity	NPC319671
0.5962	Remote Similarity	NPC476734
0.58	Remote Similarity	NPC130459
0.58	Remote Similarity	NPC474221
0.5738	Remote Similarity	NPC282559
0.5714	Remote Similarity	NPC488960
0.5636	Remote Similarity	NPC180199
0.5636	Remote Similarity	NPC477919
0.5636	Remote Similarity	NPC600598
0.5536	Remote Similarity	NPC215893
0.5517	Remote Similarity	NPC472505
0.537	Remote Similarity	NPC488498
0.537	Remote Similarity	NPC61952
0.537	Remote Similarity	NPC603184
0.5294	Remote Similarity	NPC27243
0.5294	Remote Similarity	NPC476737
0.5273	Remote Similarity	NPC248758
0.5246	Remote Similarity	NPC480086
0.5167	Remote Similarity	NPC211403
0.5156	Remote Similarity	NPC609700
0.5091	Remote Similarity	NPC99154
0.5091	Remote Similarity	NPC201027
0.5091	Remote Similarity	NPC279241
0.5091	Remote Similarity	NPC481630
0.5088	Remote Similarity	NPC91369
0.5079	Remote Similarity	NPC257942

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC234897 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6815
0.1-0.2	2256
0.2-0.3	78
0.3-0.4	0
0.4-0.5	0
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	NPD4224	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