NPASS Compound

Natural Product: NPC3439

Natural Product ID	NPC3439
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(-)-Surinamensinol A
IUPAC Name	(1R,2R)-2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1-(3,4,5-trimethoxyphenyl)propan-1-ol
Synonyms	(-)-Surinamensinol A
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2088626
PubChem CID	70687027
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds

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 59 60 0 0 0 0 0 0 0 0999 V2000 -1.0680 -3.1644 -0.3869 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7973 -2.1559 0.7186 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.1805 -1.6352 1.1565 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.7828 -0.7843 0.1151 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6556 0.6089 0.1602 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2064 1.4111 -0.8093 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8972 0.7967 -1.8404 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0567 -0.5702 -1.9387 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4806 -1.3400 -0.9334 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7582 -1.1207 -2.9925 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9995 -2.4681 -3.2256 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4500 1.5903 -2.8116 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6795 1.9180 -3.9493 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0925 2.8186 -0.7872 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3629 3.3234 0.3466 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0033 -2.6489 1.6042 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0909 -1.0620 0.3017 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0323 -0.4372 0.6555 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4063 0.7015 -0.0725 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5509 1.4067 0.2262 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3649 1.0010 1.2629 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5826 1.7884 1.5493 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7669 1.2601 0.7355 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9950 2.0850 1.0487 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7068 3.4183 0.7007 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0235 -0.1050 1.9878 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8580 -0.8152 1.6766 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5398 -1.9174 2.4180 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3586 -2.3467 3.4820 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2750 -2.6836 -1.3477 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1853 -3.8509 -0.5416 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9136 -3.8251 -0.1170 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4341 -2.7312 1.5687 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0064 -0.9808 2.0681 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1069 1.0544 0.9846 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6276 -2.4243 -1.0458 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0023 -2.5327 -3.7426 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2884 -2.9214 -3.9490 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1188 -3.0122 -2.2909 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5927 1.9871 -3.7049 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9698 2.8927 -4.4004 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7649 1.1598 -4.7624 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8487 2.9935 1.2812 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2960 3.0824 0.2737 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4374 4.4426 0.3020 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6033 -2.9759 0.8927 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7978 1.0473 -0.8867 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8002 2.2747 -0.3569 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4773 2.8681 1.3041 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8520 1.7387 2.6156 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9795 0.2138 0.9873 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5587 1.3940 -0.3616 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2351 1.9902 2.1062 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8305 1.7051 0.4250 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0081 3.4263 0.0148 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6595 -0.4179 2.7959 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5724 -1.5394 4.2208 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3015 -2.8099 3.1099 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7747 -3.1222 4.0557 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 1 0 7 12 1 0 12 13 1 0 6 14 1 0 14 15 1 0 3 16 1 0 2 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 21 26 1 0 26 27 2 0 27 28 1 0 28 29 1 0 9 4 1 0 27 18 1 0 1 30 1 0 1 31 1 0 1 32 1 0 2 33 1 1 3 34 1 1 5 35 1 0 9 36 1 0 11 37 1 0 11 38 1 0 11 39 1 0 13 40 1 0 13 41 1 0 13 42 1 0 15 43 1 0 15 44 1 0 15 45 1 0 16 46 1 0 19 47 1 0 20 48 1 0 22 49 1 0 22 50 1 0 23 51 1 0 23 52 1 0 24 53 1 0 24 54 1 0 25 55 1 0 26 56 1 0 29 57 1 0 29 58 1 0 29 59 1 0 M END

Standard InCHIKey	AWIGQZJNJGIWHL-SZNDQCEHSA-N
Standard InCHI	InChI=1S/C22H30O7/c1-14(29-17-9-8-15(7-6-10-23)11-18(17)25-2)21(24)16-12-19(26-3)22(28-5)20(13-16)27-4/h8-9,11-14,21,23-24H,6-7,10H2,1-5H3/t14-,21+/m1/s1
SMILES	C[C@H]([C@@H](c1cc(c(c(c1)OC)OC)OC)O)Oc1ccc(CCCO)cc1OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	406.2	Volume:	417.668 ? Van der Waals volume.
Dense:	0.973	LogP:	1.87 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.27 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.748 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	12.0
TPSA:	86.61 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.593	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.02	Fsp³:	0.455
MCE-18:	30.0 ? 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:	0.308	Fluc inhibitor:	0.007 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.017 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.214 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.115	Promiscuous compounds:	0.081

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.838	MDCK Permeability:	-4.708
Pgp-inhibitor:	0.532	Pgp-substrate:	0.325
PAMPA:	0.032 ? 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):	0.0
20% Bioavailability (F20%):	0.063	30% Bioavailability (F30%):	0.017
50% Bioavailability (F50%):	0.519

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.536	MRP1:	0.986
Plasma Protein Binding (PPB):	76.297%	Volume Distribution (VD):	-0.16
Fu:	23.434% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.867
OATP1B3 inhibitor:	0.976	BCRP inhibitor:	0.158
BSEP inhibitor:	0.994

ADMET: Metabolism

CYP1A2-inhibitor:	0.055	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.542	CYP2C9-substrate:	0.024
CYP2D6-inhibitor:	0.975	CYP2D6-substrate:	0.055
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.002
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.001 ? 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):

7.907

Half-life (T1/2):

1.314

ADMET: Toxicity

hERG Blockers:	0.293	hERG Blockers (10um):	0.444
Human Hepatotoxicity (H-HT):	0.719	Drug-induced Liver Injury (DILI):	0.424
AMES Toxicity:	0.306	Rat Oral Acute Toxicity:	0.113
Maximum Recommended Daily Dose:	0.224	Skin Sensitization:	0.587
Carcinogencity:	0.288	Eye Corrosion:	0.033
Eye Irritation:	0.88	Respiratory Toxicity:	0.602
Drug-induced Neurotoxicity:	0.598	Ototoxicity:	0.667
Hematotoxicity:	0.458	Drug-induced Nephrotoxicity:	0.641
Genotoxicity:	0.046	RPMI-8226 Immunitoxicity:	0.129
A549 Cytotoxicity:	0.382	Hek293 Cytotoxicity:	0.411
BCF:	0.765 ? 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:	3.053 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.389 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.524 ? 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
NPO25682	Acorus calamus	Species	Acoraceae	Eukaryota	n.a.	rhizome	n.a.	PMID[21563811]
NPO5681	Acorus gramineus	Species	Acoraceae	Eukaryota	n.a.	rhizome	n.a.	PMID[21936523]
NPO5681	Acorus gramineus	Species	Acoraceae	Eukaryota	Rhizomes	n.a.	n.a.	PMID[21936523]
NPO25682	Acorus calamus	Species	Acoraceae	Eukaryota	rhizomes	n.a.	n.a.	PMID[22671987]
NPO5681	Acorus gramineus	Species	Acoraceae	Eukaryota	rhizomes	n.a.	n.a.	PMID[22951040]
NPO25682	Acorus calamus	Species	Acoraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23373216]
NPO25682	Acorus calamus	Species	Acoraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[35872238]
NPO5681	Acorus gramineus	Species	Acoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25682	Acorus calamus	Species	Acoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5681	Acorus gramineus	Species	Acoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO25682	Acorus calamus	Species	Acoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO5681	Acorus gramineus	Species	Acoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO25682	Acorus calamus	Species	Acoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO25682	Acorus calamus	Species	Acoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO5681	Acorus gramineus	Species	Acoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO25682	Acorus calamus	Species	Acoraceae	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
IC50	5
Activity	1

Activity Type	# Activity
Cell line	6

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	IC50	=	4170.0	nM	PMID[22951040]
NPT147	Cell line	SK-MEL-2	Homo sapiens	IC50	=	14210.0	nM	PMID[22951040]
NPT34	Cell line	BV-2	Mus musculus	IC50	=	17910.0	nM	PMID[22951040]
NPT148	Cell line	HCT-15	Homo sapiens	IC50	=	24330.0	nM	PMID[22951040]
NPT146	Cell line	SK-OV-3	Homo sapiens	IC50	=	26180.0	nM	PMID[22951040]
NPT34	Cell line	BV-2	Mus musculus	Activity	=	88.8	%	PMID[22951040]

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 NPC3439 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	15569
0.1-0.2	30562
0.2-0.3	3464
0.3-0.4	190
0.4-0.5	44
0.5-0.6	17
0.6-0.7	8
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	NPC285339
0.625	Remote Similarity	NPC469613
0.625	Remote Similarity	NPC30043
0.625	Remote Similarity	NPC469625
0.6226	Remote Similarity	NPC473091
0.6226	Remote Similarity	NPC273295
0.6226	Remote Similarity	NPC222004
0.6226	Remote Similarity	NPC602870
0.6222	Remote Similarity	NPC137685
0.5965	Remote Similarity	NPC293701
0.5962	Remote Similarity	NPC71090
0.5818	Remote Similarity	NPC190629
0.5769	Remote Similarity	NPC202582
0.5769	Remote Similarity	NPC243749
0.5741	Remote Similarity	NPC469612
0.5741	Remote Similarity	NPC469614
0.5667	Remote Similarity	NPC111247
0.5667	Remote Similarity	NPC292056
0.5556	Remote Similarity	NPC63083
0.5179	Remote Similarity	NPC473090
0.5179	Remote Similarity	NPC94276
0.5179	Remote Similarity	NPC109822
0.5179	Remote Similarity	NPC605984
0.5088	Remote Similarity	NPC470258
0.5082	Remote Similarity	NPC194519
0.5082	Remote Similarity	NPC484134

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC3439 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2868
0.1-0.2	5836
0.2-0.3	426
0.3-0.4	19
0.4-0.5	1
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