NPASS Compound

Natural Product: NPC481671

Natural Product ID	NPC481671
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	XCPRSBVYFBCRJC-PDAIFWRYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	21777784
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] 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 74 74 0 0 0 0 0 0 0 0999 V2000 0.5729 0.6863 -1.0160 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8006 -0.1385 -2.2012 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1762 -0.7794 -2.7987 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5465 -0.7800 -2.4168 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2915 -1.5278 -3.2036 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2556 -0.1044 -1.3189 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7076 -0.5977 -1.3511 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6656 0.2867 -1.5239 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1164 -0.0264 -1.5784 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8927 0.7352 -0.5851 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6034 1.8532 -1.0454 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3497 2.5985 -0.1695 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4100 2.2557 1.1793 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7170 1.1629 1.6381 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7357 0.7411 3.0422 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9584 0.4098 0.7356 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2700 -0.6846 1.2331 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9771 -0.5849 1.7585 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.0754 3.7189 -0.5702 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0118 -2.0286 -1.2044 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1354 -0.2157 -2.8013 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1385 -0.8897 -1.9542 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4309 -0.3173 -0.6110 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5579 -1.1888 -0.0023 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9613 -2.5974 0.0359 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8063 -0.8061 1.3788 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8297 -0.9508 2.2414 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0165 -0.2785 1.9123 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1541 -0.0155 1.3187 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3270 0.5448 2.0606 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5699 1.9852 1.6620 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5227 -0.3149 1.7178 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0616 0.4843 3.4319 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6738 -1.1286 -0.7802 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2030 1.4696 -1.2470 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3358 0.0867 -0.1405 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5003 1.2988 -0.8129 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0889 -1.3837 -3.6883 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9170 -0.3752 -0.3204 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2841 0.9988 -1.4628 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3585 1.3451 -1.6364 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4948 0.2074 -2.6154 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3075 -1.1075 -1.4605 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5463 2.1050 -2.0804 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0074 2.8613 1.8487 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5986 1.1681 3.5955 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8391 -0.3838 3.0546 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8311 0.9822 3.6157 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4301 0.2809 1.3581 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4128 -1.5529 1.6493 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0827 -0.4792 2.8747 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6986 4.6575 -0.5091 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9033 -2.2394 -0.5896 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2037 -2.4442 -2.2205 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1081 -2.5119 -0.7680 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0598 -0.6769 -3.8265 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5373 0.8150 -3.0384 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8930 -2.0052 -1.8452 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0867 -0.9531 -2.5888 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5904 -0.4890 0.0885 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7521 0.7248 -0.6113 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3455 -3.1570 0.9200 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8626 -2.5891 0.1071 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2573 -3.1500 -0.8738 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0214 -0.0433 3.0158 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2761 -0.1919 0.2843 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5236 2.6280 2.5458 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8669 2.2937 0.8604 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5951 2.0537 1.2484 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3871 -1.3122 2.1802 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4765 0.1612 2.0280 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5017 -0.4915 0.6181 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8576 0.2544 3.9606 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6124 -0.3619 -1.4067 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 2 0 4 6 1 0 6 7 1 0 7 8 2 0 8 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 1 0 14 16 2 0 16 17 1 0 17 18 1 0 12 19 1 0 7 20 1 0 2 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 24 26 1 0 26 27 2 0 26 28 1 0 28 29 2 0 29 30 1 0 30 31 1 0 30 32 1 0 30 33 1 0 24 34 1 0 16 10 1 0 1 35 1 0 1 36 1 0 1 37 1 0 3 38 1 0 6 39 1 0 6 40 1 0 8 41 1 0 9 42 1 0 9 43 1 0 11 44 1 0 13 45 1 0 15 46 1 0 15 47 1 0 15 48 1 0 18 49 1 0 18 50 1 0 18 51 1 0 19 52 1 0 20 53 1 0 20 54 1 0 20 55 1 0 21 56 1 0 21 57 1 0 22 58 1 0 22 59 1 0 23 60 1 0 23 61 1 0 25 62 1 0 25 63 1 0 25 64 1 0 28 65 1 0 29 66 1 0 31 67 1 0 31 68 1 0 31 69 1 0 32 70 1 0 32 71 1 0 32 72 1 0 33 73 1 0 34 74 1 0 M END

Standard InCHIKey	XCPRSBVYFBCRJC-PDAIFWRYSA-N
Standard InCHI	InChI=1S/C28H40O6/c1-19(9-8-13-28(6,33)25(31)12-14-27(4,5)32)15-23(29)16-20(2)10-11-22-18-24(30)17-21(3)26(22)34-7/h10,12,14-15,17-18,30,32-33H,8-9,11,13,16H2,1-7H3/b14-12+,19-15+,20-10+
SMILES	C/C(=CC(=O)C/C(=C/Cc1cc(cc(C)c1OC)O)/C)/CCCC(C)(C(=O)/C=C/C(C)(C)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	472.28	Volume:	515.937 ? Van der Waals volume.
Dense:	0.915	LogP:	4.243 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.389 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.833 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	13.0	Rigid Bonds:	11.0
TPSA:	104.06 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	1.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.278	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.961	Fsp³:	0.5
MCE-18:	34.0 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.485	Fluc inhibitor:	0.133 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.004 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.526 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.321	Promiscuous compounds:	0.058

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.25	MDCK Permeability:	-4.913
Pgp-inhibitor:	0.181	Pgp-substrate:	0.005
PAMPA:	0.156 ? 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):	0.005
20% Bioavailability (F20%):	0.705	30% Bioavailability (F30%):	0.907
50% Bioavailability (F50%):	0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.824
Plasma Protein Binding (PPB):	96.019%	Volume Distribution (VD):	-0.089
Fu:	3.149% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.991
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.099
BSEP inhibitor:	0.979

ADMET: Metabolism

CYP1A2-inhibitor:	0.928	CYP1A2-substrate:	0.997
CYP2C19-inhibitor:	0.781	CYP2C19-substrate:	0.266
CYP2C9-inhibitor:	0.342	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.061	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.974	CYP3A4-substrate:	0.863
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.996 ? 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):

6.269

Half-life (T1/2):

0.874

ADMET: Toxicity

hERG Blockers:	0.176	hERG Blockers (10um):	0.324
Human Hepatotoxicity (H-HT):	0.828	Drug-induced Liver Injury (DILI):	0.067
AMES Toxicity:	0.386	Rat Oral Acute Toxicity:	0.246
Maximum Recommended Daily Dose:	0.826	Skin Sensitization:	0.891
Carcinogencity:	0.577	Eye Corrosion:	0.0
Eye Irritation:	0.049	Respiratory Toxicity:	0.715
Drug-induced Neurotoxicity:	0.147	Ototoxicity:	0.801
Hematotoxicity:	0.464	Drug-induced Nephrotoxicity:	0.762
Genotoxicity:	0.903	RPMI-8226 Immunitoxicity:	0.205
A549 Cytotoxicity:	0.262	Hek293 Cytotoxicity:	0.814
BCF:	1.926 ? 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:	4.667 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.072 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.477 ? 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
NPO11992	Cystoseira usneoides	Species	Sargassaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23458950]
NPO11992	Cystoseira usneoides	Species	Sargassaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11992	Cystoseira usneoides	Species	Sargassaceae	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
Inhibition	1
Ratio EC50	1
EC50	1

Activity Type	# Activity
Cell line	1
Others	1
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
NPT1970	Cell line	THP-1	Homo sapiens	Inhibition	=	64.0	%	PMID[23458950]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	EC50	=	33100.0	nM	PMID[23458950]
NPT2	Others	Unspecified	n.a.	Ratio EC50	=	0.78	n.a.	PMID[23458950]

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 NPC481671 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	10756
0.1-0.2	36047
0.2-0.3	2973
0.3-0.4	52
0.4-0.5	22
0.5-0.6	0
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	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC481670
0.7727	Intermediate Similarity	NPC481669
0.7727	Intermediate Similarity	NPC481668
0.7258	Intermediate Similarity	NPC290710
0.7258	Intermediate Similarity	NPC32500
0.6351	Remote Similarity	NPC601412
0.6351	Remote Similarity	NPC610791
0.6351	Remote Similarity	NPC611328

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC481671 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3415
0.1-0.2	5677
0.2-0.3	58
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