NPASS Compound

Natural Product: NPC14650

Natural Product ID	NPC14650
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Sarcotin H
IUPAC Name	(5Z)-5-[(Z,2R)-9-[(5S)-5-(furan-3-ylmethyl)-5-methoxy-2-oxofuran-3-yl]-2,6-dimethylnon-5-enylidene]-4-hydroxy-3-methylfuran-2-one
Synonyms	Sarcotin H
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL484051
PubChem CID	54704222
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000254] Ethers [CHEMONTID:0001656] Acetals [CHEMONTID:0004472] Ketals

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 67 0 0 0 0 0 0 0 0999 V2000 -6.0681 -2.3871 -1.4008 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8958 -2.0462 -0.0643 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3541 -0.7882 0.1034 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.2535 0.3327 -0.3760 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5375 0.3358 0.3620 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6828 -0.3314 0.0014 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.6343 -0.0962 0.9054 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.1709 0.6935 1.8434 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8571 0.9888 1.5404 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2355 -0.5943 1.5091 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9107 -0.3608 1.8219 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4052 -0.1420 2.9746 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1554 -0.4057 0.5836 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9770 -0.6525 -0.4230 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6664 -0.1979 0.5029 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3395 1.1778 1.0323 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1840 1.3417 0.9302 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5293 1.2030 -0.4755 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3191 0.3150 -1.0443 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9814 -0.7116 -0.2249 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4750 -0.6343 -0.1309 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2876 -0.7519 -1.3217 C 0 0 2 0 0 0 0 0 0 0 0 0 5.7493 -0.6968 -1.1857 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4409 -0.3835 -0.1424 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8961 -0.0342 1.0671 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9062 0.2389 1.9621 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7888 0.5882 3.1563 O 0 0 0 0 0 0 0 0 0 0 0 0 8.1599 0.0512 1.2780 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8887 -0.3193 0.0251 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8270 -0.5989 -0.9610 O 0 0 0 0 0 0 0 0 0 0 0 0 9.5373 0.2214 1.8094 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9677 0.2462 -2.4215 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1067 2.2184 -1.4080 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5097 -3.4038 -1.4286 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1004 -2.4733 -1.9390 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7683 -1.6958 -1.8705 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4234 0.3161 -1.4619 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7050 1.2792 -0.1582 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7931 -0.9457 -0.8719 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7141 1.0674 2.7247 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1665 1.6075 2.0874 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6991 -0.7424 -1.4635 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3653 -0.3292 -0.5364 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1332 -0.9483 1.1188 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6388 1.1886 2.1053 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8741 1.9579 0.4912 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3845 2.3984 1.2960 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6191 0.6956 1.6642 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4373 0.3690 -2.1417 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4910 -0.7640 0.7699 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6567 -1.6947 -0.6890 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6489 0.2551 0.5197 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7442 -1.4792 0.5874 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0859 -1.7379 -1.8005 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3003 -0.9518 -2.0832 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8721 -1.5086 -1.3941 H 0 0 0 0 0 0 0 0 0 0 0 0 10.2758 0.2864 0.9890 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8104 -0.7145 2.3762 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6359 1.1282 2.4210 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9432 0.5157 -2.9454 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3861 -0.1951 -3.2586 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6137 1.2120 -2.0482 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7340 1.7390 -2.1612 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7493 2.7892 -1.8670 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7172 2.9593 -0.8603 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 3 2 1 1 3 4 1 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 1 0 8 9 2 0 3 10 1 0 10 11 1 0 11 12 2 0 11 13 1 0 13 14 2 0 13 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 1 0 26 27 2 0 26 28 1 0 28 29 2 0 29 30 1 0 28 31 1 0 22 32 1 0 18 33 1 0 14 3 1 0 29 24 1 0 9 5 1 0 1 34 1 0 1 35 1 0 1 36 1 0 4 37 1 0 4 38 1 0 6 39 1 0 8 40 1 0 9 41 1 0 14 42 1 0 15 43 1 0 15 44 1 0 16 45 1 0 16 46 1 0 17 47 1 0 17 48 1 0 19 49 1 0 20 50 1 0 20 51 1 0 21 52 1 0 21 53 1 0 22 54 1 6 23 55 1 0 30 56 1 0 31 57 1 0 31 58 1 0 31 59 1 0 32 60 1 0 32 61 1 0 32 62 1 0 33 63 1 0 33 64 1 0 33 65 1 0 M END

Standard InCHIKey	VBKLXPVCFCAJHW-KYZQRXNCSA-N
Standard InCHI	InChI=1S/C26H32O7/c1-17(7-5-9-18(2)13-22-23(27)19(3)24(28)32-22)8-6-10-21-15-26(30-4,33-25(21)29)14-20-11-12-31-16-20/h7,11-13,15-16,18,27H,5-6,8-10,14H2,1-4H3/b17-7-,22-13-/t18-,26+/m1/s1
SMILES	CO[C@@]1(Cc2cocc2)OC(=O)C(=C1)CCC/C(=CCC[C@H](/C=C/1OC(=O)C(=C1O)C)C)/C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	456.21	Volume:	473.023 ? Van der Waals volume.
Dense:	0.964	LogP:	5.384 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.061 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.828 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	19.0
TPSA:	95.2 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.349	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.644	Fsp³:	0.462
MCE-18:	64.105 ? 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:	0.763	Fluc inhibitor:	0.053 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.047 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.529 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.339	Promiscuous compounds:	0.078

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.436	MDCK Permeability:	-5.088
Pgp-inhibitor:	0.54	Pgp-substrate:	0.002
PAMPA:	0.237 ? 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):	0.197
20% Bioavailability (F20%):	0.741	30% Bioavailability (F30%):	0.983
50% Bioavailability (F50%):	0.859

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.91
Plasma Protein Binding (PPB):	98.252%	Volume Distribution (VD):	-0.158
Fu:	1.664% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.98
OATP1B3 inhibitor:	0.902	BCRP inhibitor:	0.004
BSEP inhibitor:	0.979

ADMET: Metabolism

CYP1A2-inhibitor:	0.064	CYP1A2-substrate:	0.965
CYP2C19-inhibitor:	0.027	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.422	CYP2C9-substrate:	0.032
CYP2D6-inhibitor:	0.002	CYP2D6-substrate:	0.989
CYP3A4-inhibitor:	0.327	CYP3A4-substrate:	0.941
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.995
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):

4.758

Half-life (T1/2):

0.778

ADMET: Toxicity

hERG Blockers:	0.084	hERG Blockers (10um):	0.236
Human Hepatotoxicity (H-HT):	0.647	Drug-induced Liver Injury (DILI):	0.936
AMES Toxicity:	0.378	Rat Oral Acute Toxicity:	0.553
Maximum Recommended Daily Dose:	0.776	Skin Sensitization:	1.0
Carcinogencity:	0.431	Eye Corrosion:	0.003
Eye Irritation:	0.788	Respiratory Toxicity:	0.303
Drug-induced Neurotoxicity:	0.23	Ototoxicity:	0.344
Hematotoxicity:	0.246	Drug-induced Nephrotoxicity:	0.912
Genotoxicity:	0.692	RPMI-8226 Immunitoxicity:	0.093
A549 Cytotoxicity:	0.042	Hek293 Cytotoxicity:	0.179
BCF:	1.586 ? 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:	4.76 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.137 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.691 ? 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
NPO33064	sarcotragus sp.	Species	Irciniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11678655]
NPO33064	sarcotragus sp.	Species	Irciniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[12350153]
NPO33064	sarcotragus sp.	Species	Irciniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18341287]

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
ED50	5

Activity Type	# Activity
Cell line	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
NPT81	Cell line	A549	Homo sapiens	ED50	=	6.7	ug ml-1	PMID[16038534]
NPT146	Cell line	SK-OV-3	Homo sapiens	ED50	=	6.8	ug ml-1	PMID[13678412]
NPT147	Cell line	SK-MEL-2	Homo sapiens	ED50	=	5.9	ug ml-1	PMID[13678412]
NPT574	Cell line	XF498	Homo sapiens	ED50	=	6.3	ug ml-1	PMID[13678412]
NPT148	Cell line	HCT-15	Homo sapiens	ED50	=	6.1	ug ml-1	PMID[13678412]

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 NPC14650 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	9282
0.1-0.2	39093
0.2-0.3	1415
0.3-0.4	29
0.4-0.5	21
0.5-0.6	10
0.6-0.7	6
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8889	High Similarity	NPC288209
0.726	Intermediate Similarity	NPC474136
0.6711	Remote Similarity	NPC476351
0.6494	Remote Similarity	NPC283284
0.6494	Remote Similarity	NPC289911
0.6447	Remote Similarity	NPC71274
0.6447	Remote Similarity	NPC75557
0.6125	Remote Similarity	NPC474279
0.5765	Remote Similarity	NPC489596
0.5455	Remote Similarity	NPC261733
0.5455	Remote Similarity	NPC307346
0.5455	Remote Similarity	NPC489598
0.5395	Remote Similarity	NPC475739
0.5281	Remote Similarity	NPC267004
0.5281	Remote Similarity	NPC489597
0.5281	Remote Similarity	NPC218712
0.5227	Remote Similarity	NPC489595
0.5158	Remote Similarity	NPC487126

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC14650 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3459
0.1-0.2	5667
0.2-0.3	24
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