NPASS Compound

Natural Product: NPC475848

Natural Product ID	NPC475848
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Polyfibrospongol A Monoacetate
IUPAC Name	methyl 3-[[(1R,2S,4aS,8aS)-1,2,4a-trimethyl-5-methylidene-3,4,6,7,8,8a-hexahydro-2H-naphthalen-1-yl]methyl]-4-acetyloxy-5-methoxybenzoate
Synonyms	polyfibrospongol A monoacetate
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL517296
PubChem CID	10646199
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0002279] Benzene and substituted derivatives [CHEMONTID:0000176] Benzoic acids and derivatives [CHEMONTID:0002344] Methoxybenzoic acids and derivatives [CHEMONTID:0002347] M-methoxybenzoic acids and derivatives

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 69 0 0 0 0 0 0 0 0999 V2000 -1.4872 -1.6203 3.1001 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9287 -1.2134 1.6873 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1746 -0.4277 1.8205 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5098 0.5888 0.8125 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5546 0.8919 -0.2732 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3972 -0.0932 -0.3565 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8317 -0.4126 0.9934 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6397 0.8112 1.8837 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4621 -1.1238 0.9972 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6178 -0.4423 0.3751 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9462 -0.4953 -0.9488 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0276 0.2425 -1.4330 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8083 1.0421 -0.6345 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4870 1.1010 0.7077 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4221 0.3772 1.1906 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2987 1.9383 1.5788 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2711 2.6059 1.1559 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9874 2.0013 2.9292 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7268 2.7907 3.8454 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2921 0.1357 -2.7898 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3714 0.8631 -3.3215 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2229 -1.2908 -1.8646 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6573 -2.5806 -2.0386 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6679 -2.9784 -1.3770 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0176 -3.5725 -2.9664 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7994 -1.3308 -1.1137 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2496 -1.6207 -1.2482 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0499 -0.4711 -1.8096 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2448 0.7587 -1.5904 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1810 1.6217 -2.5844 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1000 2.3363 -0.2424 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6269 -2.3065 3.0928 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2744 -0.7785 3.7516 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3550 -2.1623 3.5859 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0114 -2.1722 1.1504 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2396 -0.0047 2.8716 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0203 -1.1861 1.8440 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5512 0.4193 0.3959 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6785 1.5700 1.3704 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6211 0.4349 -0.9336 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0257 1.5711 1.4243 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5715 1.1320 2.3838 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0211 0.4408 2.7679 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3885 -2.1910 0.6584 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7576 -1.2560 2.0879 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6478 1.6059 -1.0467 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2510 0.4793 2.2589 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7809 2.3430 4.8620 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1607 3.7493 3.9668 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7534 3.0299 3.4641 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0582 1.9470 -3.2712 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5785 0.6264 -4.3815 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3070 0.6777 -2.7535 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8724 -4.1043 -3.4769 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4078 -4.2967 -2.3767 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4416 -3.0716 -3.7671 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4225 -1.2391 -2.1888 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3083 -2.2592 -0.7546 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7487 -2.1084 -0.3957 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3093 -2.4293 -2.0524 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2731 -0.6248 -2.8971 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0368 -0.4379 -1.3253 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7105 1.4701 -3.5271 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5770 2.5098 -2.4763 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9477 2.9894 -0.6343 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2722 2.4534 -0.9333 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9386 2.7463 0.7705 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 7 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 14 16 1 0 16 17 2 0 16 18 1 0 18 19 1 0 12 20 1 0 20 21 1 0 11 22 1 0 22 23 1 0 23 24 2 0 23 25 1 0 6 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 2 0 5 31 1 0 7 2 1 0 29 5 1 0 15 10 1 0 1 32 1 0 1 33 1 0 1 34 1 0 2 35 1 0 3 36 1 0 3 37 1 0 4 38 1 0 4 39 1 0 6 40 1 0 8 41 1 0 8 42 1 0 8 43 1 0 9 44 1 0 9 45 1 0 13 46 1 0 15 47 1 0 19 48 1 0 19 49 1 0 19 50 1 0 21 51 1 0 21 52 1 0 21 53 1 0 25 54 1 0 25 55 1 0 25 56 1 0 26 57 1 0 26 58 1 0 27 59 1 0 27 60 1 0 28 61 1 0 28 62 1 0 30 63 1 0 30 64 1 0 31 65 1 0 31 66 1 0 31 67 1 0 M END

Standard InCHIKey	ZFRLLXLAQUFWHD-MCRPIMJISA-N
Standard InCHI	InChI=1S/C26H36O5/c1-16-9-8-10-22-25(16,4)12-11-17(2)26(22,5)15-20-13-19(24(28)30-7)14-21(29-6)23(20)31-18(3)27/h13-14,17,22H,1,8-12,15H2,2-7H3/t17-,22+,25+,26+/m0/s1
SMILES	CC1CCC2(C(C1(C)CC3=C(C(=CC(=C3)C(=O)OC)OC)OC(=O)C)CCCC2=C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	428.26	Volume:	460.715 ? Van der Waals volume.
Dense:	0.93	LogP:	4.75 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.931 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.837 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	20.0
TPSA:	61.83 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.339	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.014	Fsp³:	0.615
MCE-18:	82.286 ? 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:	0.055	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.028 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.413 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.241	Promiscuous compounds:	0.007

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.709	MDCK Permeability:	-4.675
Pgp-inhibitor:	0.987	Pgp-substrate:	0.0
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):	0.0
20% Bioavailability (F20%):	0.001	30% Bioavailability (F30%):	0.003
50% Bioavailability (F50%):	0.276

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.969	MRP1:	1.0
Plasma Protein Binding (PPB):	96.817%	Volume Distribution (VD):	0.217
Fu:	2.673% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.365
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.249
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.991	CYP1A2-substrate:	0.978
CYP2C19-inhibitor:	0.732	CYP2C19-substrate:	0.864
CYP2C9-inhibitor:	0.283	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.03	CYP2D6-substrate:	0.387
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.002
CYP2B6-substrate:	0.059	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

7.036

Half-life (T1/2):

0.239

ADMET: Toxicity

hERG Blockers:	0.045	hERG Blockers (10um):	0.496
Human Hepatotoxicity (H-HT):	0.284	Drug-induced Liver Injury (DILI):	0.596
AMES Toxicity:	0.134	Rat Oral Acute Toxicity:	0.322
Maximum Recommended Daily Dose:	0.699	Skin Sensitization:	0.541
Carcinogencity:	0.19	Eye Corrosion:	0.014
Eye Irritation:	0.609	Respiratory Toxicity:	0.428
Drug-induced Neurotoxicity:	0.701	Ototoxicity:	0.415
Hematotoxicity:	0.186	Drug-induced Nephrotoxicity:	0.056
Genotoxicity:	0.015	RPMI-8226 Immunitoxicity:	0.054
A549 Cytotoxicity:	0.445	Hek293 Cytotoxicity:	0.265
BCF:	1.978 ? 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:	5.148 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.388 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.07 ? 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
NPO4760	Polyfibrospongia australis	n.a.	n.a.	n.a.	n.a.	Taiwan	n.a.	PMID[9051909]
NPO4760	Polyfibrospongia australis	n.a.	n.a.	n.a.	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
IC50	3

Activity Type	# Activity
Cell line	2
Non-molecular	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
NPT168	Cell line	P388	Mus musculus	IC50	=	3.4	ug.mL-1	PMID[24530492]
NPT81	Cell line	A549	Homo sapiens	IC50	=	3.1	ug.mL-1	DOI[10.6019/CHEMBL1201861]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	2.1	ug.mL-1	PMID[9051909]

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 NPC475848 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	11223
0.1-0.2	37563
0.2-0.3	1014
0.3-0.4	30
0.4-0.5	13
0.5-0.6	12
0.6-0.7	1
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
0.9344	High Similarity	NPC474306
0.7826	Intermediate Similarity	NPC474305
0.6479	Remote Similarity	NPC124842
0.5942	Remote Similarity	NPC489118
0.5833	Remote Similarity	NPC290286
0.5694	Remote Similarity	NPC75295
0.5676	Remote Similarity	NPC604728
0.5556	Remote Similarity	NPC489120
0.5479	Remote Similarity	NPC489114
0.5455	Remote Similarity	NPC62051
0.5455	Remote Similarity	NPC606953
0.5455	Remote Similarity	NPC611058
0.527	Remote Similarity	NPC176590
0.5205	Remote Similarity	NPC489119
0.519	Remote Similarity	NPC470042

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC475848 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4134
0.1-0.2	4956
0.2-0.3	60
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