NPASS Compound

Natural Product: NPC476008

Natural Product ID	NPC476008
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Sergeolide
IUPAC Name	n.a.
Synonyms	Sergeolide; Sergiolide
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL521373
PubChem CID	44575805
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0002119] Quassinoids

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 64 69 0 0 0 0 0 0 0 0999 V2000 1.5010 3.9528 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7062 2.6807 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2760 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 -1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8578 -2.6401 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 -0.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1470 1.7537 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8351 3.2209 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2617 2.7574 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4086 3.6844 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0967 5.1517 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2114 6.1554 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6380 5.6918 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2481 4.3215 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7399 4.4783 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0517 5.9455 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7527 6.6955 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4408 8.1628 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0143 8.6263 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7024 10.0935 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8995 7.6226 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6496 9.6482 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0404 10.2101 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2224 9.2866 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2491 11.6955 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9635 5.0040 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0239 5.1527 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9499 4.2246 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5875 2.4047 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.2480 3.3369 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4221 6.5556 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5789 8.0474 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.6356 5.6740 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.0059 6.2841 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2959 5.2249 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7731 3.1579 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4591 5.0319 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0969 2.1188 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7760 0.0000 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4190 0.9587 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6212 2.1234 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3403 1.2595 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6426 3.3432 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9509 4.3184 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8473 6.3174 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4031 5.1256 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1480 6.7893 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7517 4.2170 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5600 2.8543 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0647 7.4227 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9224 8.3974 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4579 13.1809 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7345 11.4867 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7637 11.9042 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0073 4.7836 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6012 2.8626 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1155 3.2805 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4757 1.1960 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7479 3.3188 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.3762 6.8942 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.6160 4.9137 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3958 7.6544 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 5 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 1 1 10 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 1 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 21 23 1 0 20 24 1 0 24 25 1 0 25 26 2 0 25 27 1 0 18 28 1 0 28 29 1 0 29 30 1 0 29 31 1 0 28 32 1 0 18 33 1 1 33 34 2 0 33 35 1 0 35 36 1 0 12 2 1 0 23 14 1 0 8 3 1 0 30 10 1 0 30 15 1 0 19 15 1 0 1 37 1 0 1 38 1 0 1 39 1 0 2 40 1 1 4 41 1 0 9 42 1 0 11 43 1 0 11 44 1 0 11 45 1 0 12 46 1 6 13 47 1 0 13 48 1 0 14 49 1 1 16 50 1 0 16 51 1 0 19 52 1 1 20 53 1 6 27 54 1 0 27 55 1 0 27 56 1 0 28 57 1 1 29 58 1 1 30 59 1 6 31 60 1 0 32 61 1 0 36 62 1 0 36 63 1 0 36 64 1 0 M END

Standard InCHIKey	ZZKFDOQILIXHHH-UAXMYPJESA-N
Standard InCHI	InChI=1S/C25H28O11/c1-9-11-5-15(27)35-13(11)7-23(3)12(9)6-14-24-8-33-25(22(31)32-4,20(29)16(28)18(23)24)19(24)17(21(30)36-14)34-10(2)26/h5,7,9,12,14,16-20,28-29H,6,8H2,1-4H3/t9-,12+,14-,16-,17-,18-,19-,20+,23+,24-,25-/m1/s1
SMILES	C[C@@H]1C2=CC(=O)OC2=C[C@@]2(C)[C@H]1C[C@@H]1[C@]34CO[C@]([C@@H]4[C@H](C(=O)O1)OC(=O)C)([C@H]([C@@H]([C@H]23)O)O)C(=O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	504.16	Volume:	470.491 ? Van der Waals volume.
Dense:	1.072	LogP:	1.02 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.536 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.492 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	31.0
TPSA:	154.89 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	2.0	Rings:	6.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.379	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.724	Fsp³:	0.68
MCE-18:	148.381 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.56	Fluc inhibitor:	0.035 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.239 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.087	Promiscuous compounds:	0.591

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.71	MDCK Permeability:	-5.121
Pgp-inhibitor:	0.159	Pgp-substrate:	0.681
PAMPA:	0.807 ? 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):	0.025
20% Bioavailability (F20%):	0.728	30% Bioavailability (F30%):	0.975
50% Bioavailability (F50%):	0.953

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.942
Plasma Protein Binding (PPB):	61.038%	Volume Distribution (VD):	-0.205
Fu:	38.211% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.001
BSEP inhibitor:	0.342

ADMET: Metabolism

CYP1A2-inhibitor:	0.035	CYP1A2-substrate:	0.015
CYP2C19-inhibitor:	0.146	CYP2C19-substrate:	0.253
CYP2C9-inhibitor:	0.022	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.517
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.888
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.954 ? 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):

3.59

Half-life (T1/2):

2.696

ADMET: Toxicity

hERG Blockers:	0.012	hERG Blockers (10um):	0.096
Human Hepatotoxicity (H-HT):	0.71	Drug-induced Liver Injury (DILI):	0.967
AMES Toxicity:	0.842	Rat Oral Acute Toxicity:	0.793
Maximum Recommended Daily Dose:	0.788	Skin Sensitization:	1.0
Carcinogencity:	0.413	Eye Corrosion:	0.002
Eye Irritation:	0.542	Respiratory Toxicity:	0.559
Drug-induced Neurotoxicity:	0.688	Ototoxicity:	0.433
Hematotoxicity:	0.487	Drug-induced Nephrotoxicity:	0.941
Genotoxicity:	0.998	RPMI-8226 Immunitoxicity:	0.23
A549 Cytotoxicity:	0.215	Hek293 Cytotoxicity:	0.407
BCF:	0.584 ? 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:	3.395 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.065 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.446 ? 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
NPO33214	cedronia granatensis	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[1517739]
NPO4057	Picrolemma pseudocoffea	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[6533270]
NPO4057	Picrolemma pseudocoffea	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4057	Picrolemma pseudocoffea	Species	n.a.	n.a.	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
T/C	1
GI50	1
IC50	1

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	T/C	=	169.0	%	PMID[6533270]
NPT165	Cell line	HeLa	Homo sapiens	IC50	<	1000.0	nM	PMID[10869203]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	GI50	=	3.8	nM	PMID[19199792]

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 NPC476008 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	16406
0.1-0.2	31405
0.2-0.3	1975
0.3-0.4	21
0.4-0.5	9
0.5-0.6	35
0.6-0.7	6
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
0.641	Remote Similarity	NPC479018
0.6203	Remote Similarity	NPC89929
0.6049	Remote Similarity	NPC146432
0.6049	Remote Similarity	NPC470778
0.6026	Remote Similarity	NPC213084
0.6024	Remote Similarity	NPC480785
0.5952	Remote Similarity	NPC94509
0.5934	Remote Similarity	NPC190065
0.5909	Remote Similarity	NPC475636
0.5833	Remote Similarity	NPC480787
0.5833	Remote Similarity	NPC480784
0.5823	Remote Similarity	NPC470776
0.5823	Remote Similarity	NPC17772
0.5806	Remote Similarity	NPC141215
0.5747	Remote Similarity	NPC480786
0.5747	Remote Similarity	NPC470779
0.5745	Remote Similarity	NPC479019
0.5684	Remote Similarity	NPC295885
0.567	Remote Similarity	NPC471089
0.5652	Remote Similarity	NPC602216
0.5625	Remote Similarity	NPC140045
0.5595	Remote Similarity	NPC18945
0.5595	Remote Similarity	NPC152301
0.5595	Remote Similarity	NPC480783
0.5556	Remote Similarity	NPC143268
0.5529	Remote Similarity	NPC190185
0.5521	Remote Similarity	NPC54614
0.5465	Remote Similarity	NPC67251
0.5455	Remote Similarity	NPC480777
0.5422	Remote Similarity	NPC485623
0.5402	Remote Similarity	NPC479017
0.5402	Remote Similarity	NPC265557
0.5366	Remote Similarity	NPC470777
0.5361	Remote Similarity	NPC480779
0.5341	Remote Similarity	NPC476729
0.5333	Remote Similarity	NPC105926
0.53	Remote Similarity	NPC480778
0.5294	Remote Similarity	NPC24651
0.5263	Remote Similarity	NPC309096
0.5238	Remote Similarity	NPC323821
0.5176	Remote Similarity	NPC16081

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476008 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6294
0.1-0.2	2823
0.2-0.3	33
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