NPASS Compound

Natural Product: NPC471461

Natural Product ID	NPC471461
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Xerophilusin Iv
IUPAC Name	n.a.
Synonyms	xerophilusin IV
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL251231
PubChem CID	23626811
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 2D 54 58 0 0 0 0 0 0 0 0999 V2000 3.7981 -0.6697 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6491 -1.6339 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 -2.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6491 -3.5623 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 -3.8971 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 -3.8971 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 -2.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6491 0.9642 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 2.5981 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2954 0.6125 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3828 -0.5621 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0000 2.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 2.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0905 3.1111 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7372 3.5163 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8940 5.0080 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4381 2.7663 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9322 3.3764 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2077 -1.1827 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7461 -2.6569 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9916 -0.2857 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7981 -4.5264 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8321 -4.8203 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7461 -2.5393 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0865 -4.5781 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4895 -5.3743 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4895 -5.3743 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1595 -4.4101 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6491 -3.5623 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9183 -2.1098 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2388 -1.1162 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9183 -0.4882 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0586 0.4512 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0000 2.5981 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7580 -0.8169 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6491 0.9642 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0861 -1.3808 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4095 -0.5130 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2863 -1.4724 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8991 2.2632 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8991 0.3349 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7500 3.8971 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3953 4.0944 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1700 4.5883 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6804 5.8897 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2643 5.6181 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 3 2 1 6 3 4 1 0 3 5 1 0 5 6 1 0 6 7 1 0 8 7 1 6 8 9 1 0 9 10 1 0 10 11 1 0 10 12 1 0 12 13 1 1 12 14 1 0 14 15 1 0 12 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 20 23 1 0 23 24 2 0 23 25 1 0 25 26 2 0 9 3 1 0 16 25 1 1 15 8 1 0 21 16 1 0 17 8 1 0 1 27 1 0 2 28 1 0 2 29 1 0 4 30 1 0 4 31 1 0 4 32 1 0 5 33 1 0 5 34 1 0 6 35 1 0 6 36 1 0 7 37 1 0 7 38 1 0 9 39 1 1 10 40 1 6 11 41 1 0 13 42 1 0 15 43 1 0 15 44 1 0 17 45 1 1 18 46 1 0 18 47 1 0 19 48 1 0 19 49 1 0 20 50 1 6 21 51 1 6 22 52 1 0 24 53 1 0 24 54 1 0 M END

Standard InCHIKey	HSNHHKCWUXSXSA-IZZIWLOZSA-N
Standard InCHI	InChI=1S/C20H28O6/c1-10-11-4-5-12-18-7-3-6-17(2,8-21)13(18)16(24)20(25,26-9-18)19(12,14(10)22)15(11)23/h11-13,15-16,21,23-25H,1,3-9H2,2H3/t11-,12-,13+,15+,16-,17-,18+,19-,20-/m0/s1
SMILES	OC[C@]1(C)CCC[C@@]23[C@@H]1[C@H](O)[C@](O)(OC2)[C@@]12[C@H]3CC[C@H]([C@H]2O)C(=C)C1=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	364.19	Volume:	359.162 ? Van der Waals volume.
Dense:	1.014	LogP:	1.145 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.656 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.662 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	24.0
TPSA:	107.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	6.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.501	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.915	Fsp³:	0.85
MCE-18:	129.568 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.161	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.017 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.002 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.141	Promiscuous compounds:	0.571

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.556	MDCK Permeability:	-4.781
Pgp-inhibitor:	0.0	Pgp-substrate:	0.753
PAMPA:	0.996 ? 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):	0.675
20% Bioavailability (F20%):	0.939	30% Bioavailability (F30%):	0.982
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.006	MRP1:	0.62
Plasma Protein Binding (PPB):	56.077%	Volume Distribution (VD):	-0.151
Fu:	47.604% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.973
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.016
BSEP inhibitor:	0.004

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.009
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.022
CYP2C9-inhibitor:	0.015	CYP2C9-substrate:	0.007
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.015	CYP3A4-substrate:	0.292
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.475
HLM stability:	0.275 ? 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):

5.681

Half-life (T1/2):

1.901

ADMET: Toxicity

hERG Blockers:	0.041	hERG Blockers (10um):	0.159
Human Hepatotoxicity (H-HT):	0.574	Drug-induced Liver Injury (DILI):	0.278
AMES Toxicity:	0.901	Rat Oral Acute Toxicity:	0.393
Maximum Recommended Daily Dose:	0.268	Skin Sensitization:	0.996
Carcinogencity:	0.874	Eye Corrosion:	0.002
Eye Irritation:	0.883	Respiratory Toxicity:	0.513
Drug-induced Neurotoxicity:	0.135	Ototoxicity:	0.622
Hematotoxicity:	0.325	Drug-induced Nephrotoxicity:	0.576
Genotoxicity:	0.617	RPMI-8226 Immunitoxicity:	0.123
A549 Cytotoxicity:	0.2	Hek293 Cytotoxicity:	0.739
BCF:	0.984 ? 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:	3.375 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.846 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.078 ? 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
NPO8404	Isodon xerophilus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10843567]
NPO8404	Isodon xerophilus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17665952]
NPO8404	Isodon xerophilus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[33325237]
NPO8404	Isodon xerophilus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8404	Isodon xerophilus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8404	Isodon xerophilus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8404	Isodon xerophilus	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

Activity Type	# Activity
IC50	3

Activity Type	# Activity
Cell line	3

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
NPT111	Cell line	K562	Homo sapiens	IC50	>	10000.0	nM	PMID[17844994]
NPT1097	Cell line	MKN-45	Homo sapiens	IC50	>	10000.0	nM	PMID[20498315]
NPT65	Cell line	HepG2	Homo sapiens	IC50	>	10000.0	nM	PMID[20498315]

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 NPC471461 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	18637
0.1-0.2	27419
0.2-0.3	3595
0.3-0.4	132
0.4-0.5	43
0.5-0.6	14
0.6-0.7	10
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	Natural Product ID
0.7818	Intermediate Similarity	NPC488145
0.7719	Intermediate Similarity	NPC102741
0.7321	Intermediate Similarity	NPC488144
0.7321	Intermediate Similarity	NPC483202
0.7167	Intermediate Similarity	NPC488148
0.7143	Intermediate Similarity	NPC488146
0.6949	Remote Similarity	NPC488143
0.6552	Remote Similarity	NPC55973
0.6552	Remote Similarity	NPC89860
0.6552	Remote Similarity	NPC189663
0.6552	Remote Similarity	NPC153234
0.6102	Remote Similarity	NPC252679
0.6102	Remote Similarity	NPC118721
0.6032	Remote Similarity	NPC145625
0.6032	Remote Similarity	NPC488142
0.6032	Remote Similarity	NPC213320
0.5873	Remote Similarity	NPC471093
0.5833	Remote Similarity	NPC473352
0.5606	Remote Similarity	NPC474927
0.5455	Remote Similarity	NPC29505
0.5312	Remote Similarity	NPC488154
0.5312	Remote Similarity	NPC488157
0.5224	Remote Similarity	NPC56656
0.5156	Remote Similarity	NPC287676
0.5156	Remote Similarity	NPC471476
0.5156	Remote Similarity	NPC473324
0.5152	Remote Similarity	NPC471244
0.5077	Remote Similarity	NPC63244
0.5077	Remote Similarity	NPC122339
0.5077	Remote Similarity	NPC483201

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC471461 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6456
0.1-0.2	2641
0.2-0.3	53
0.3-0.4	0
0.4-0.5	0
0.5-0.6	0
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
		NPD

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