NPASS Compound

Natural Product: NPC51404

Natural Product ID	NPC51404
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Heraclenol
IUPAC Name	9-[(2R)-2,3-dihydroxy-3-methylbutoxy]furo[3,2-g]chromen-7-one
Synonyms	Heraclenol
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1173444
PubChem CID	73253
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000145] Coumarins and derivatives [CHEMONTID:0000358] Furanocoumarins [CHEMONTID:0002569] Linear furanocoumarins [CHEMONTID:0000202] Psoralens

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 38 40 0 0 0 0 0 0 0 0999 V2000 2.6914 4.1689 -0.3642 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8466 2.9152 -0.1746 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1386 2.4954 0.0518 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3445 1.1590 0.2593 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2422 0.3378 0.2253 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9777 0.8370 -0.0082 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8059 2.1234 -0.2044 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8810 0.0031 -0.0397 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4099 0.4295 -0.2668 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2770 0.8252 0.8020 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6029 1.2308 0.2059 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.3011 0.1013 -0.4877 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5336 0.5855 -0.9381 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6261 -0.9926 0.5249 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5307 -0.4902 -1.6199 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4070 2.2905 -0.6708 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1053 -1.3484 0.1722 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3637 -1.8438 0.4044 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4508 -1.0088 0.4344 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2522 -3.2259 0.5763 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9096 -3.4847 0.4348 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2715 -2.3823 0.2022 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9738 3.2065 0.0655 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3490 0.7834 0.4419 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8087 1.7323 1.2373 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3605 0.0671 1.5775 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2763 1.5920 1.0124 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3265 1.3732 -1.4977 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5279 -1.5308 0.2182 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8118 -0.4931 1.4808 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7742 -1.6908 0.6485 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8319 0.1886 -2.1124 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2832 -0.7929 -2.4053 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0507 -1.4652 -1.3183 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7936 2.1007 -1.4027 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4387 -1.4302 0.6211 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0655 -3.9160 0.7762 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4256 -4.4507 0.5016 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 12 14 1 0 12 15 1 0 11 16 1 0 8 17 2 0 17 18 1 0 18 19 2 0 18 20 1 0 20 21 2 0 21 22 1 0 7 2 1 0 22 17 1 0 19 5 1 0 3 23 1 0 4 24 1 0 10 25 1 0 10 26 1 0 11 27 1 1 13 28 1 0 14 29 1 0 14 30 1 0 14 31 1 0 15 32 1 0 15 33 1 0 15 34 1 0 16 35 1 0 19 36 1 0 20 37 1 0 21 38 1 0 M END

Standard InCHIKey	FOINLJRVEBYARJ-LLVKDONJSA-N
Standard InCHI	InChI=1S/C16H16O6/c1-16(2,19)11(17)8-21-15-13-10(5-6-20-13)7-9-3-4-12(18)22-14(9)15/h3-7,11,17,19H,8H2,1-2H3/t11-/m1/s1
SMILES	O=c1ccc2c(o1)c(OC[C@H](C(O)(C)C)O)c1c(c2)cco1

Calculated Properties

Physi-Chem Properties

MedChem Properties

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

ADMET: Distribution

ADMET: Metabolism

ADMET: Excretion

ADMET: Toxicity

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	n.a.	root	n.a.	DOI[10.5012/bkcs.2003.24.11.1699]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	n.a.	root	n.a.	PMID[12510838]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	n.a.	root	n.a.	PMID[15646793]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21625478]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	n.a.	root	n.a.	PMID[21657081]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27444348]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	Roots	n.a.	n.a.	PMID[31464439]
NPO662	Angelica officinalis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO662	Angelica officinalis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO662	Angelica officinalis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO662	Angelica officinalis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24758	Angelica dahurica	Species	Apiaceae	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
Potency	4
IC50	1
Inhibition	1
ED50	1
EC50	1

Activity Type	# Activity
Individual protein	5
Organism	1
Non-molecular	1
Others	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT10	Individual protein	Geminin	Homo sapiens	Potency	n.a.	11.6	nM	PubChem BioAssay data set
NPT484	Individual protein	Luciferin 4-monooxygenase	Photinus pyralis	Potency	n.a.	23934.1	nM	PubChem BioAssay data set
NPT740	Individual protein	Beta-secretase 1	Homo sapiens	IC50	>	500000.0	nM	PMID[22222157]
NPT740	Individual protein	Beta-secretase 1	Homo sapiens	Inhibition	=	17.2	%	PMID[22222157]
NPT5	Individual protein	Histone-lysine N-methyltransferase, H3 lysine-9 specific 3	Homo sapiens	Potency	n.a.	1412.5	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	>	100.0	ug ml-1	DOI[10.1021/np50015a016]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	EC50	=	380.0	nM	PMID[20187635]
NPT2	Others	Unspecified	n.a.	Potency	=	461.1	nM	PubChem BioAssay data set

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 NPC51404 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	23262
0.1-0.2	25666
0.2-0.3	669
0.3-0.4	212
0.4-0.5	29
0.5-0.6	9
0.6-0.7	6
0.7-0.8	0
0.8-0.85	1
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	NPC83421
0.8113	Intermediate Similarity	NPC215722
0.7959	Intermediate Similarity	NPC487850
0.7143	Intermediate Similarity	NPC173149
0.7143	Intermediate Similarity	NPC179015
0.6964	Remote Similarity	NPC243509
0.6863	Remote Similarity	NPC33320
0.6842	Remote Similarity	NPC602724
0.678	Remote Similarity	NPC224165
0.6154	Remote Similarity	NPC478570
0.6	Remote Similarity	NPC216092
0.5909	Remote Similarity	NPC478569
0.5634	Remote Similarity	NPC478632
0.5556	Remote Similarity	NPC478631
0.5469	Remote Similarity	NPC107244
0.5455	Remote Similarity	NPC198876
0.541	Remote Similarity	NPC479800
0.5397	Remote Similarity	NPC303210
0.5397	Remote Similarity	NPC95472
0.5397	Remote Similarity	NPC239270

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC51404 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4545
0.1-0.2	4492
0.2-0.3	106
0.3-0.4	5
0.4-0.5	1
0.5-0.6	0
0.6-0.7	1
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
0.6863	Remote Similarity	NPD919	Phase 4

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