NPASS Compound

Natural Product: NPC316560

Natural Product ID	NPC316560
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Isodrummondin D
IUPAC Name	n.a.
Synonyms	Isodrummondin D
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL483235
PubChem CID	NA
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000123] Benzopyrans [CHEMONTID:0003410] 1-benzopyrans [CHEMONTID:0003522] 2,2-dimethyl-1-benzopyrans

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 68 70 0 0 0 0 0 0 0 0999 V2000 7.2625 -0.0596 -0.8749 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0022 -0.2814 -0.1295 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2014 0.7238 0.1476 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9213 0.5705 0.8923 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7314 1.0353 0.0455 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9457 2.5012 -0.2977 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5435 0.9532 0.9027 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5014 0.1799 0.6528 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6228 0.1766 1.5705 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9297 0.5747 0.9897 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1560 1.9122 0.6733 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1290 2.8158 0.9065 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3573 2.3441 0.1437 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5603 3.7657 -0.1787 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6217 4.5713 0.0376 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8175 4.2687 -0.7416 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3929 1.4654 -0.0970 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1857 0.1381 0.2108 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9688 -0.2994 0.7476 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7951 -1.6257 1.0450 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7650 -2.6014 0.8434 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0179 -3.2741 2.1973 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2734 -3.6995 -0.1015 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0370 -2.0973 0.2743 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2437 -0.8317 -0.0227 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6122 1.8780 -0.6303 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5175 -0.6432 -0.5379 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4216 -1.3973 -0.8455 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6647 -0.6290 -1.4600 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6688 0.1729 -1.1375 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7556 0.1726 -2.0307 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7226 -1.4401 -2.6683 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7213 -1.4074 -3.4420 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5678 -2.3202 -2.9794 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5489 1.7631 2.0557 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6613 -1.6602 0.2987 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1632 -0.4279 -0.3077 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4623 1.0173 -1.0562 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2480 -0.5904 -1.8606 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4692 1.7209 -0.1735 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9634 1.1745 1.8268 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7209 -0.4981 1.1091 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7120 2.6468 -1.0688 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3053 2.9884 0.6295 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9881 2.9802 -0.5568 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8064 -0.8487 2.0146 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4252 0.8028 2.4918 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4838 3.1086 0.1839 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6860 4.1318 -0.0336 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7416 5.3626 -0.8721 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0509 3.8508 -1.7419 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0260 -3.7062 2.1752 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2624 -4.0678 2.2988 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9070 -2.4745 2.9636 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3228 -4.1361 0.2433 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0451 -4.4840 -0.1084 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1471 -3.3047 -1.1291 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8132 -2.8310 0.1068 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1974 -0.5487 -0.4331 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4758 1.8395 -0.1356 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8459 1.0335 -2.5820 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3735 -1.7585 -3.1346 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3845 -3.0928 -2.2047 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7553 -2.9095 -3.9161 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8692 1.4297 2.9496 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5725 -2.3168 0.2359 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3430 -1.7063 1.3643 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9312 -2.1013 -0.3959 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 3 4 1 0 4 5 1 0 5 6 1 0 5 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 11 13 1 0 13 14 1 0 14 15 2 0 14 16 1 0 13 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 1 0 21 22 1 0 21 23 1 0 21 24 1 0 24 25 2 0 17 26 1 0 8 27 1 0 27 28 2 0 27 29 1 0 29 30 2 0 30 31 1 0 29 32 1 0 32 33 2 0 32 34 1 0 7 35 1 0 2 36 1 0 30 5 1 0 19 10 1 0 25 18 1 0 1 37 1 0 1 38 1 0 1 39 1 0 3 40 1 0 4 41 1 0 4 42 1 0 6 43 1 0 6 44 1 0 6 45 1 0 9 46 1 0 9 47 1 0 12 48 1 0 16 49 1 0 16 50 1 0 16 51 1 0 22 52 1 0 22 53 1 0 22 54 1 0 23 55 1 0 23 56 1 0 23 57 1 0 24 58 1 0 25 59 1 0 26 60 1 0 31 61 1 0 34 62 1 0 34 63 1 0 34 64 1 0 35 65 1 0 36 66 1 0 36 67 1 0 36 68 1 0 M END

Standard InCHIKey	QDEXSBYEIYRPIT-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C28H32O8/c1-13(2)8-11-28(7)25(34)18(23(33)20(15(4)30)26(28)35)12-17-22(32)19(14(3)29)21(31)16-9-10-27(5,6)36-24(16)17/h8-10,31-32,34-35H,11-12H2,1-7H3
SMILES	CC(=CCC1(C)C(=C(Cc2c(O)c(C(=O)C)c(c3c2OC(C)(C)C=C3)O)C(=O)C(=C1O)C(=O)C)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	496.21	Volume:	511.132 ? Van der Waals volume.
Dense:	0.971	LogP:	3.238 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.124 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.788 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	21.0
TPSA:	141.36 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.24	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.231	Fsp³:	0.393
MCE-18:	89.974 ? 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:	0.555	Fluc inhibitor:	0.068 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.502 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.852 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.418	Promiscuous compounds:	0.255

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.214	MDCK Permeability:	-4.779
Pgp-inhibitor:	0.34	Pgp-substrate:	0.0
PAMPA:	0.979 ? 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):	0.016
20% Bioavailability (F20%):	0.623	30% Bioavailability (F30%):	0.848
50% Bioavailability (F50%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.064	MRP1:	0.996
Plasma Protein Binding (PPB):	98.043%	Volume Distribution (VD):	-0.039
Fu:	1.941% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.978	BCRP inhibitor:	0.014
BSEP inhibitor:	0.975

ADMET: Metabolism

CYP1A2-inhibitor:	0.061	CYP1A2-substrate:	0.722
CYP2C19-inhibitor:	0.004	CYP2C19-substrate:	0.221
CYP2C9-inhibitor:	0.006	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	0.029	CYP3A4-substrate:	0.007
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.945
HLM stability:	0.998 ? 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):

0.999

Half-life (T1/2):

1.421

ADMET: Toxicity

hERG Blockers:	0.007	hERG Blockers (10um):	0.053
Human Hepatotoxicity (H-HT):	0.545	Drug-induced Liver Injury (DILI):	0.83
AMES Toxicity:	0.249	Rat Oral Acute Toxicity:	0.64
Maximum Recommended Daily Dose:	0.137	Skin Sensitization:	0.84
Carcinogencity:	0.113	Eye Corrosion:	0.0
Eye Irritation:	0.557	Respiratory Toxicity:	0.937
Drug-induced Neurotoxicity:	0.016	Ototoxicity:	0.703
Hematotoxicity:	0.528	Drug-induced Nephrotoxicity:	0.732
Genotoxicity:	0.88	RPMI-8226 Immunitoxicity:	0.107
A549 Cytotoxicity:	0.143	Hek293 Cytotoxicity:	0.055
BCF:	1.429 ? 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:	4.732 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.599 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.155 ? 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
NPO28558	Hypericum drummondii	Species	Hypericaceae	Eukaryota	n.a.	root	n.a.	PMID[1800634]
NPO28558	Hypericum drummondii	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[2746258]
NPO28558	Hypericum drummondii	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28558	Hypericum drummondii	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28558	Hypericum drummondii	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28558	Hypericum drummondii	Species	Hypericaceae	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
MIC	3

Activity Type	# Activity
Organism	3

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
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	=	0.2	ug.mL-1	PMID[1800634]
NPT602	Organism	Mycobacterium smegmatis	Mycobacterium smegmatis	MIC	=	1.56	ug.mL-1	PMID[1800634]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	0.78	ug.mL-1	PMID[1800634]

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 NPC316560 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	13545
0.1-0.2	34250
0.2-0.3	1898
0.3-0.4	144
0.4-0.5	9
0.5-0.6	6
0.6-0.7	4
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
0.7838	Intermediate Similarity	NPC321629
0.7761	Intermediate Similarity	NPC316911
0.68	Remote Similarity	NPC481985
0.6538	Remote Similarity	NPC481986
0.6375	Remote Similarity	NPC321148
0.6145	Remote Similarity	NPC323884
0.5915	Remote Similarity	NPC268178
0.5867	Remote Similarity	NPC325346
0.5797	Remote Similarity	NPC328983
0.5541	Remote Similarity	NPC180501
0.5465	Remote Similarity	NPC326193
0.5325	Remote Similarity	NPC54820

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC316560 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5296
0.1-0.2	3838
0.2-0.3	15
0.3-0.4	1
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