NPASS Compound

Natural Product: NPC489288

Natural Product ID	NPC489288
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	LWTIZOHDKCIZPP-XHEWZUHNSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	21590534
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001552] Sesterterpenoids [CHEMONTID:0002881] Cheilanthane sesterterpenoids

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 70 0 0 0 0 0 0 0 0999 V2000 2.4884 -2.0969 -1.9574 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7439 -1.8669 -0.9093 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9330 -3.0082 -0.3446 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5111 -2.5682 -0.2082 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6866 -1.1581 0.2742 C 0 0 1 0 0 0 0 0 0 0 0 0 0.1080 -0.2049 -0.5686 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0050 -0.4624 -2.0468 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1847 1.2326 -0.3126 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6667 1.4631 -0.5035 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3363 0.6834 0.5853 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.7748 1.0666 0.7674 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5525 1.1144 -0.5378 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7193 2.5272 1.2664 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4930 0.2942 1.8045 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9653 -1.0353 2.1700 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5323 -1.2885 1.8912 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1055 -0.8052 0.4917 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.0196 -1.5041 -0.4602 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5613 -0.5484 -0.2308 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5599 0.4845 -0.4381 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8984 0.1170 0.0942 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9085 1.2153 -0.1595 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6125 2.3381 -0.7743 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8216 3.1283 -0.8279 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8917 4.2796 -1.3583 O 0 0 0 0 0 0 0 0 0 0 0 0 6.8473 2.4324 -0.2217 O 0 0 0 0 0 0 0 0 0 0 0 0 6.3248 1.2130 0.2203 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5031 1.1057 1.6002 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4462 -1.0533 -0.3537 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4821 -3.1260 -2.3704 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1025 -1.4105 -2.5111 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3989 -3.3304 0.5917 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9640 -3.8303 -1.0668 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0480 -2.7735 -1.1635 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9628 -3.2469 0.5576 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1989 -1.1372 1.2984 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1165 -1.5441 -2.2982 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8953 0.0301 -2.5220 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8728 -0.0521 -2.5455 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4335 1.8404 -0.9888 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0250 1.4754 0.7679 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8333 2.5457 -0.2510 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0277 1.2277 -1.5086 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8228 1.0014 1.5444 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5354 0.5705 -0.4032 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8766 2.1581 -0.8095 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9982 0.7460 -1.4016 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7193 3.2009 0.3840 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7045 2.7064 1.7761 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8590 2.6863 1.9273 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6493 0.8772 2.7625 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5534 0.1413 1.4356 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5534 -1.8724 1.6861 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1076 -1.2439 3.2742 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3223 -2.3650 1.9257 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8573 -0.8093 2.6383 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8739 -2.6100 -0.2787 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8176 -1.3404 -1.5135 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0882 -1.3333 -0.2211 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5832 -0.8292 0.8880 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6064 0.8390 -1.4988 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2322 1.3914 0.1613 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8843 0.0766 1.2346 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6190 2.5938 -1.1619 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8075 0.3496 -0.2879 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7733 0.2073 1.8785 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2628 -0.9055 -0.8821 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 6 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 11 13 1 0 11 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 6 6 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 24 26 1 0 26 27 1 0 27 28 1 0 21 29 1 0 19 2 1 0 27 22 1 0 17 5 1 0 17 10 1 0 1 30 1 0 1 31 1 0 3 32 1 0 3 33 1 0 4 34 1 0 4 35 1 0 5 36 1 1 7 37 1 0 7 38 1 0 7 39 1 0 8 40 1 0 8 41 1 0 9 42 1 0 9 43 1 0 10 44 1 1 12 45 1 0 12 46 1 0 12 47 1 0 13 48 1 0 13 49 1 0 13 50 1 0 14 51 1 0 14 52 1 0 15 53 1 0 15 54 1 0 16 55 1 0 16 56 1 0 18 57 1 0 18 58 1 0 18 59 1 0 19 60 1 1 20 61 1 0 20 62 1 0 21 63 1 0 23 64 1 0 27 65 1 0 28 66 1 0 29 67 1 0 M END

Standard InCHIKey	LWTIZOHDKCIZPP-XHEWZUHNSA-N
Standard InCHI	InChI=1S/C25H38O4/c1-15-7-8-20-24(4,12-9-19-23(2,3)10-6-11-25(19,20)5)17(15)14-18(26)16-13-21(27)29-22(16)28/h13,17-20,22,26,28H,1,6-12,14H2,2-5H3/t17-,18?,19+,20+,22?,24+,25+/m1/s1
SMILES	C=C1CC[C@H]2[C@@](C)(CC[C@H]3C(C)(C)CCC[C@]23C)[C@@H]1CC(C1=CC(=O)OC1O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	402.28	Volume:	433.982 ? Van der Waals volume.
Dense:	0.927	LogP:	3.632 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.635 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.798 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	23.0
TPSA:	66.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.528	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.816	Fsp³:	0.8
MCE-18:	76.044 ? 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:	0.534	Fluc inhibitor:	0.028 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.013 ? 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:	0.214	Promiscuous compounds:	0.04

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.638	MDCK Permeability:	-4.788
Pgp-inhibitor:	0.092	Pgp-substrate:	0.0
PAMPA:	0.334 ? 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):	0.001
20% Bioavailability (F20%):	0.006	30% Bioavailability (F30%):	0.077
50% Bioavailability (F50%):	0.682

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.031	MRP1:	0.064
Plasma Protein Binding (PPB):	97.819%	Volume Distribution (VD):	0.106
Fu:	2.83% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.199
BSEP inhibitor:	0.882

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.003
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.005	CYP2C9-substrate:	0.06
CYP2D6-inhibitor:	0.998	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.999	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.035
HLM stability:	0.217 ? 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):

7.132

Half-life (T1/2):

1.158

ADMET: Toxicity

hERG Blockers:	0.051	hERG Blockers (10um):	0.403
Human Hepatotoxicity (H-HT):	0.658	Drug-induced Liver Injury (DILI):	0.761
AMES Toxicity:	0.607	Rat Oral Acute Toxicity:	0.559
Maximum Recommended Daily Dose:	0.893	Skin Sensitization:	0.97
Carcinogencity:	0.947	Eye Corrosion:	0.007
Eye Irritation:	0.765	Respiratory Toxicity:	0.817
Drug-induced Neurotoxicity:	0.35	Ototoxicity:	0.608
Hematotoxicity:	0.573	Drug-induced Nephrotoxicity:	0.93
Genotoxicity:	0.652	RPMI-8226 Immunitoxicity:	0.071
A549 Cytotoxicity:	0.188	Hek293 Cytotoxicity:	0.585
BCF:	2.219 ? 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:	5.137 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.958 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.488 ? 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
NPO32608	ircinia sp.	Species	Irciniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11277743]
NPO32608	ircinia sp.	Species	Irciniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11908961]
NPO32608	ircinia sp.	Species	Irciniidae	Eukaryota	n.a.	Okinawan	n.a.	PMID[12608859]
NPO32608	ircinia sp.	Species	Irciniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18163586]
NPO32608	ircinia sp.	Species	Irciniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[7769397]
NPO32608	ircinia sp.	Species	Irciniidae	Eukaryota	n.a.	Okinawan	n.a.	PMID[7853011]

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	2

Activity Type	# Activity
Individual protein	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1613	Individual protein	Ribosomal protein S6 kinase alpha 5	Homo sapiens	IC50	=	4000.0	nM	PMID[11277743]
NPT1441	Individual protein	MAP kinase-activated protein kinase 2	Homo sapiens	IC50	=	90000.0	nM	PMID[11277743]

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 NPC489288 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	16030
0.1-0.2	27452
0.2-0.3	5743
0.3-0.4	500
0.4-0.5	106
0.5-0.6	18
0.6-0.7	6
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	2
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.94	High Similarity	NPC472809
0.94	High Similarity	NPC472810
0.6724	Remote Similarity	NPC311070
0.6724	Remote Similarity	NPC475709
0.6552	Remote Similarity	NPC472812
0.6441	Remote Similarity	NPC489285
0.6167	Remote Similarity	NPC177037
0.6167	Remote Similarity	NPC472814
0.5932	Remote Similarity	NPC478392
0.5932	Remote Similarity	NPC251528
0.5873	Remote Similarity	NPC489287
0.5789	Remote Similarity	NPC484730
0.5789	Remote Similarity	NPC185587
0.5789	Remote Similarity	NPC484729
0.569	Remote Similarity	NPC35655
0.5588	Remote Similarity	NPC324078
0.5574	Remote Similarity	NPC217394
0.5484	Remote Similarity	NPC79027
0.5246	Remote Similarity	NPC99321
0.5238	Remote Similarity	NPC472811
0.5167	Remote Similarity	NPC484731
0.5167	Remote Similarity	NPC189745
0.5167	Remote Similarity	NPC175334
0.5161	Remote Similarity	NPC12170
0.5082	Remote Similarity	NPC478390
0.5079	Remote Similarity	NPC470255

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC489288 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6329
0.1-0.2	2688
0.2-0.3	126
0.3-0.4	5
0.4-0.5	2
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