NPASS Compound

Natural Product: NPC474860

Natural Product ID	NPC474860
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Acantholide B
IUPAC Name	3-[(3E,7E)-4,8-dimethyl-10-(2,6,6-trimethyl-3-oxocyclohexen-1-yl)deca-3,7-dienyl]-2-hydroxy-2H-furan-5-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL485661
PubChem CID	11223324
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0001538] Diterpene lactones

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 65 66 0 0 0 0 0 0 0 0999 V2000 -4.1000 -1.0686 -1.9042 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3878 0.0684 -0.9952 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0377 -0.0045 0.3057 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3708 1.1941 1.1463 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7566 1.7002 0.7858 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0020 1.9786 -0.6358 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0379 1.2708 -1.5014 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7743 1.6963 -2.6694 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4420 0.7778 2.5933 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4407 2.3581 0.9411 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4462 -1.2442 0.8056 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0281 -1.2912 1.1832 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0177 -1.1181 0.1375 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1192 -2.1094 -0.1021 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9045 -1.9816 -1.1320 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3171 -2.0850 -0.5742 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3077 -1.9496 -1.6534 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2079 -1.0086 -1.6903 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4584 0.0816 -0.7454 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8670 -0.0014 -0.1517 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0749 1.1144 0.7928 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9971 2.0527 0.7038 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9009 2.9883 1.8156 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6153 4.0017 2.0521 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8508 2.5473 2.5862 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2869 1.3901 2.0182 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3936 0.3478 2.9382 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2514 -2.9630 -2.7527 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9163 0.1011 -0.6846 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8317 -1.8767 -1.6053 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3767 -0.8178 -2.9446 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0684 -1.4232 -1.8834 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0142 2.5780 1.3900 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4738 0.8914 1.1135 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8179 3.0699 -0.8080 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0528 1.7909 -0.9643 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1425 1.6185 3.2772 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9027 -0.1448 2.8425 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5096 0.5695 2.9050 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4573 2.2009 1.4626 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2831 2.5832 -0.1398 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8412 3.3008 1.3656 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5647 -2.0391 -0.0151 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1147 -1.7103 1.6129 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8571 -2.3100 1.6630 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7438 -0.5924 2.0091 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1978 -2.9913 0.5019 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7997 -2.8557 -1.8323 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8479 -1.0574 -1.7389 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4725 -3.1108 -0.1165 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4948 -1.3217 0.1955 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8940 -1.0328 -2.5730 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7402 0.1657 0.0534 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4093 1.0646 -1.3084 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6050 0.0630 -0.9825 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9496 -0.9851 0.3653 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7545 2.1639 -0.0728 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2285 1.6019 1.7470 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3679 0.2390 3.1128 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6855 -2.5727 -3.6221 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7298 -3.8862 -2.4275 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2977 -3.2194 -3.0344 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0921 0.5802 -0.5334 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9994 -0.2338 -1.7476 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6760 0.8556 -0.5324 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 2 0 4 9 1 0 4 10 1 0 3 11 1 0 11 12 1 0 12 13 1 0 13 14 2 3 14 15 1 0 15 16 1 0 16 17 1 0 17 18 2 3 18 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 1 0 26 27 1 0 17 28 1 0 13 29 1 0 7 2 1 0 26 21 1 0 1 30 1 0 1 31 1 0 1 32 1 0 5 33 1 0 5 34 1 0 6 35 1 0 6 36 1 0 9 37 1 0 9 38 1 0 9 39 1 0 10 40 1 0 10 41 1 0 10 42 1 0 11 43 1 0 11 44 1 0 12 45 1 0 12 46 1 0 14 47 1 0 15 48 1 0 15 49 1 0 16 50 1 0 16 51 1 0 18 52 1 0 19 53 1 0 19 54 1 0 20 55 1 0 20 56 1 0 22 57 1 0 26 58 1 0 27 59 1 0 28 60 1 0 28 61 1 0 28 62 1 0 29 63 1 0 29 64 1 0 29 65 1 0 M END

Standard InCHIKey	XPWNPMMYRFJXQW-SCNFBCNRSA-N
Standard InCHI	InChI=1S/C25H36O4/c1-17(10-7-11-20-16-23(27)29-24(20)28)8-6-9-18(2)12-13-21-19(3)22(26)14-15-25(21,4)5/h9-10,16,24,28H,6-8,11-15H2,1-5H3/b17-10+,18-9+
SMILES	CC1=C(C(CCC1=O)(C)C)CCC(=CCCC(=CCCC2=CC(=O)OC2O)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	400.26	Volume:	443.185 ? Van der Waals volume.
Dense:	0.903	LogP:	5.532 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.203 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.716 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	15.0
TPSA:	63.6 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	1.0	Rings:	2.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.397	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.939	Fsp³:	0.6
MCE-18:	37.4 ? 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:	0.889	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.151 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.18 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.628	Promiscuous compounds:	0.005

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.694	MDCK Permeability:	-4.71
Pgp-inhibitor:	0.829	Pgp-substrate:	0.156
PAMPA:	0.312 ? 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):	0.047
20% Bioavailability (F20%):	0.013	30% Bioavailability (F30%):	0.169
50% Bioavailability (F50%):	0.803

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.092	MRP1:	0.991
Plasma Protein Binding (PPB):	98.033%	Volume Distribution (VD):	-0.192
Fu:	1.766% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.494
OATP1B3 inhibitor:	0.911	BCRP inhibitor:	0.018
BSEP inhibitor:	0.993

ADMET: Metabolism

CYP1A2-inhibitor:	0.548	CYP1A2-substrate:	0.029
CYP2C19-inhibitor:	0.999	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.995	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.361	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.135	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.94	CYP2C8-inhibitor:	0.119
HLM stability:	0.997 ? 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):

6.424

Half-life (T1/2):

0.666

ADMET: Toxicity

hERG Blockers:	0.029	hERG Blockers (10um):	0.403
Human Hepatotoxicity (H-HT):	0.482	Drug-induced Liver Injury (DILI):	0.106
AMES Toxicity:	0.197	Rat Oral Acute Toxicity:	0.167
Maximum Recommended Daily Dose:	0.818	Skin Sensitization:	0.98
Carcinogencity:	0.578	Eye Corrosion:	0.014
Eye Irritation:	0.636	Respiratory Toxicity:	0.442
Drug-induced Neurotoxicity:	0.529	Ototoxicity:	0.587
Hematotoxicity:	0.318	Drug-induced Nephrotoxicity:	0.649
Genotoxicity:	0.265	RPMI-8226 Immunitoxicity:	0.085
A549 Cytotoxicity:	0.025	Hek293 Cytotoxicity:	0.119
BCF:	1.812 ? 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:	4.819 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.545 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.865 ? 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
NPO32957	Acanthodendrilla sp.	Species	Dictyodendrillidae	Eukaryota	n.a.	n.a.	n.a.	PMID[14510593]
NPO32957	Acanthodendrilla sp.	Species	Dictyodendrillidae	Eukaryota	n.a.	Indonesia	n.a.	PMID[15568767]
NPO32957	Acanthodendrilla sp.	Species	Dictyodendrillidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18257533]
NPO33221	hyrtios communis	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	PMID[23944963]
NPO32957	Acanthodendrilla sp.	Species	Dictyodendrillidae	Eukaryota	n.a.	n.a.	n.a.	PMID[9834155]
NPO32957	Acanthodendrilla sp.	Species	Dictyodendrillidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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
IZ	5
ED50	1
IC50	2

Activity Type	# Activity
Cell line	3
Organism	5

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
NPT1864	Cell line	L5178Y	Mus musculus	ED50	>	10.0	ug ml-1	DrugMatrix in vivo data: Pathology
NPT82	Cell line	MDA-MB-231	Homo sapiens	IC50	>	10000.0	nM	DOI[10.1021/np50112a018]
NPT396	Cell line	T47D	Homo sapiens	IC50	>	10000.0	nM	PMID[18598078]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	IZ	=	12.0	mm	DOI[10.1007/s00044-012-0245-1]
NPT20	Organism	Candida albicans	Candida albicans	IZ	=	10.0	mm	PMID[15270577]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IZ	=	10.0	mm	PubChem BioAssay data set
NPT19	Organism	Escherichia coli	Escherichia coli	IZ	=	9.0	mm	DOI[10.1007/s00044-012-0025-y]
NPT1780	Organism	Davidiella tassiana	Davidiella tassiana	IZ	=	10.0	mm	DrugMatrix in vivo data: Biochemistry

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 NPC474860 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	19353
0.1-0.2	27504
0.2-0.3	2843
0.3-0.4	125
0.4-0.5	19
0.5-0.6	8
0.6-0.7	3
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
0.7347	Intermediate Similarity	NPC473756
0.6792	Remote Similarity	NPC471297
0.6604	Remote Similarity	NPC471300
0.6111	Remote Similarity	NPC471296
0.5926	Remote Similarity	NPC27205
0.5818	Remote Similarity	NPC476488
0.5818	Remote Similarity	NPC476487
0.5763	Remote Similarity	NPC471298
0.5439	Remote Similarity	NPC471302
0.541	Remote Similarity	NPC126518
0.5246	Remote Similarity	NPC324170
0.5161	Remote Similarity	NPC471301

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC474860 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6852
0.1-0.2	2249
0.2-0.3	42
0.3-0.4	5
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
0.541	Remote Similarity	NPD6400	Clinical (unspecified phase)

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