NPASS Compound

Natural Product: NPC12036

Natural Product ID	NPC12036
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	UUURWWVPMHAACP-KYJUHHDHSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	100230
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 88 94 0 0 0 0 0 0 0 0999 V2000 6.1774 -2.2656 -1.8834 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8201 -1.7784 -1.8564 N 0 0 0 0 0 0 0 0 0 0 0 0 4.5805 -0.7934 -2.8493 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1236 -0.5646 -3.0480 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3659 -0.7614 -1.7949 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9984 -0.5168 -1.8865 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2072 -0.6827 -0.7997 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7450 -1.0893 0.3854 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0944 -1.3332 0.4874 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9222 -1.1705 -0.6055 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3750 -1.4007 -0.5405 C 0 0 2 0 0 0 0 0 0 0 0 0 5.1074 -0.2039 0.0363 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1820 0.8428 0.4934 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7008 1.7685 -0.3926 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8093 2.7552 -0.0065 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4034 2.7899 1.3230 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8746 1.8721 2.2280 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7603 0.9088 1.7975 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4944 3.7897 1.7172 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2308 3.6449 1.1244 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6247 2.6313 1.4959 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8757 2.4542 0.9339 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2236 3.3637 -0.0344 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4016 4.3943 -0.4386 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1693 4.5300 0.1480 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7049 5.5424 -0.2104 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4228 6.5095 -1.1878 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6972 1.3528 1.4077 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5734 0.6456 0.4223 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.2592 -0.7940 0.2739 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1276 -1.7068 0.7892 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4156 -1.4015 1.4990 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4001 0.0197 1.8723 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9074 0.8484 0.8429 N 0 0 0 0 0 0 0 0 0 0 0 0 -5.3630 2.1737 0.9436 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8552 -3.0876 0.6705 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7297 -3.5246 0.0442 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8415 -2.6041 -0.4828 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1240 -1.2552 -0.3575 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1590 -0.4278 -0.9256 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6926 -3.0897 -1.1218 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7076 -3.3767 -2.5229 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4592 -4.9064 -0.0728 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3893 -5.8291 0.4782 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0885 -1.2497 1.4702 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4648 -1.6732 2.6995 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9265 -1.4710 -1.9779 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3375 -2.9312 -1.0148 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2753 -2.9015 -2.7903 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1607 0.1509 -2.6690 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9603 -1.2382 -3.8222 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9117 0.4532 -3.4777 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7511 -1.2578 -3.8516 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5765 -0.1975 -2.8197 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5153 -1.6597 1.4279 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5546 -2.2535 0.1336 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8143 0.1472 -0.7452 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7547 -0.5306 0.8834 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9980 1.7698 -1.4330 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4336 3.4762 -0.6975 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5385 1.9309 3.2448 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1257 0.1829 2.5436 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2465 1.9632 2.2774 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1616 3.2851 -0.5070 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6930 5.1043 -1.2040 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3954 6.9870 -1.4766 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0115 6.0857 -2.1176 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1916 7.3173 -0.7543 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2747 1.7463 2.2845 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0061 0.6310 1.9425 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4836 1.0426 -0.6138 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2605 -1.5856 0.7988 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4622 -2.0570 2.3906 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3890 0.4144 2.2197 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7296 0.1405 2.7733 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4196 2.1284 1.3524 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8414 2.8438 1.6499 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5158 2.6818 -0.0549 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5521 -3.7971 1.0837 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2816 -4.3025 -2.7061 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1101 -2.5002 -3.0631 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3530 -3.5593 -2.8019 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5375 -5.6591 1.5598 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0916 -6.8577 0.2589 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3797 -5.6397 -0.0173 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2152 -0.9896 3.1124 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3467 -1.7562 3.4706 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9080 -2.6883 2.6419 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 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 16 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 1 0 26 27 1 0 22 28 1 0 28 29 1 0 29 30 1 0 30 31 2 0 31 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 31 36 1 0 36 37 2 0 37 38 1 0 38 39 2 0 39 40 1 0 38 41 1 0 41 42 1 0 37 43 1 0 43 44 1 0 8 45 1 0 45 46 1 0 11 2 1 0 18 13 1 0 25 20 2 0 34 29 1 0 10 5 1 0 39 30 1 0 40 7 1 0 1 47 1 0 1 48 1 0 1 49 1 0 3 50 1 0 3 51 1 0 4 52 1 0 4 53 1 0 6 54 1 0 9 55 1 0 11 56 1 1 12 57 1 0 12 58 1 0 14 59 1 0 15 60 1 0 17 61 1 0 18 62 1 0 21 63 1 0 23 64 1 0 24 65 1 0 27 66 1 0 27 67 1 0 27 68 1 0 28 69 1 0 28 70 1 0 29 71 1 6 32 72 1 0 32 73 1 0 33 74 1 0 33 75 1 0 35 76 1 0 35 77 1 0 35 78 1 0 36 79 1 0 42 80 1 0 42 81 1 0 42 82 1 0 44 83 1 0 44 84 1 0 44 85 1 0 46 86 1 0 46 87 1 0 46 88 1 0 M END

Standard InCHIKey	UUURWWVPMHAACP-KYJUHHDHSA-N
Standard InCHI	InChI=1S/C38H42N2O6/c1-39-15-13-25-20-34-32(42-4)22-28(25)29(39)17-23-7-10-27(11-8-23)45-33-19-24(9-12-31(33)41-3)18-30-36-26(14-16-40(30)2)21-35(43-5)37(44-6)38(36)46-34/h7-12,19-22,29-30H,13-18H2,1-6H3/t29-,30-/m0/s1
SMILES	CN1CCc2cc3c(cc2[C@@H]1Cc1ccc(cc1)Oc1cc(ccc1OC)C[C@H]1c2c(CCN1C)cc(c(c2O3)OC)OC)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	622.3	Volume:	649.006 ? Van der Waals volume.
Dense:	0.959	LogP:	3.624 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.224 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.742 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	42.0
TPSA:	61.86 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	0.0	Rings:	9.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.238	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.879	Fsp³:	0.368
MCE-18:	129.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.997	Fluc inhibitor:	0.14 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.683 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.89 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.002	Promiscuous compounds:	0.283

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.613	MDCK Permeability:	-4.668
Pgp-inhibitor:	0.927	Pgp-substrate:	0.524
PAMPA:	0.001 ? 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%):	0.466	30% Bioavailability (F30%):	0.377
50% Bioavailability (F50%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.952	MRP1:	0.973
Plasma Protein Binding (PPB):	75.204%	Volume Distribution (VD):	0.144
Fu:	23.596% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.957
OATP1B3 inhibitor:	0.986	BCRP inhibitor:	0.945
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.993	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.05
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.213
CYP2B6-substrate:	0.979	CYP2C8-inhibitor:	0.144
HLM stability:	0.555 ? 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):

9.283

Half-life (T1/2):

2.601

ADMET: Toxicity

hERG Blockers:	0.844	hERG Blockers (10um):	0.832
Human Hepatotoxicity (H-HT):	0.582	Drug-induced Liver Injury (DILI):	0.012
AMES Toxicity:	0.643	Rat Oral Acute Toxicity:	0.603
Maximum Recommended Daily Dose:	0.95	Skin Sensitization:	0.65
Carcinogencity:	0.806	Eye Corrosion:	0.0
Eye Irritation:	0.006	Respiratory Toxicity:	0.728
Drug-induced Neurotoxicity:	0.889	Ototoxicity:	0.52
Hematotoxicity:	0.102	Drug-induced Nephrotoxicity:	0.303
Genotoxicity:	0.291	RPMI-8226 Immunitoxicity:	0.082
A549 Cytotoxicity:	0.142	Hek293 Cytotoxicity:	0.641
BCF:	2.255 ? 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:	4.524 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.995 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.346 ? 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
NPO11635	Thalictrum minus	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10924164]
NPO4520	Allium macrostemon	Species	Amaryllidaceae	Eukaryota	n.a.	leaf	n.a.	PMID[26434122]
NPO11635	Thalictrum minus	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2114.1	Thalictrum minus var. hypoleucum	Varieties	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4520	Allium macrostemon	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4520	Allium macrostemon	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11635	Thalictrum minus	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO2114.1	Thalictrum minus var. hypoleucum	Varieties	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO2596	Berberis laurina	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2114.1	Thalictrum minus var. hypoleucum	Varieties	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11635	Thalictrum minus	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4520	Allium macrostemon	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11635	Thalictrum minus	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO4520	Allium macrostemon	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO2596	Berberis laurina	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4520	Allium macrostemon	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11635	Thalictrum minus	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2114.1	Thalictrum minus var. hypoleucum	Varieties	Ranunculaceae	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

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

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 NPC12036 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	34432
0.1-0.2	14711
0.2-0.3	462
0.3-0.4	118
0.4-0.5	30
0.5-0.6	33
0.6-0.7	34
0.7-0.8	1
0.8-0.85	9
0.85-0.9	0
0.9-0.95	0
0.95-1	7

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC276890
0.9516	High Similarity	NPC76682
0.9516	High Similarity	NPC10908
0.9516	High Similarity	NPC63646
0.9516	High Similarity	NPC317145
0.9516	High Similarity	NPC198498
0.9516	High Similarity	NPC115284
0.8358	Intermediate Similarity	NPC227060
0.8261	Intermediate Similarity	NPC73492
0.8261	Intermediate Similarity	NPC299990
0.8261	Intermediate Similarity	NPC480587
0.8235	Intermediate Similarity	NPC12424
0.8235	Intermediate Similarity	NPC129518
0.8235	Intermediate Similarity	NPC251580
0.8065	Intermediate Similarity	NPC247639
0.8065	Intermediate Similarity	NPC25084
0.7857	Intermediate Similarity	NPC603853
0.7671	Intermediate Similarity	NPC185639
0.7671	Intermediate Similarity	NPC251735
0.7671	Intermediate Similarity	NPC49075
0.7671	Intermediate Similarity	NPC599951
0.7581	Intermediate Similarity	NPC317439
0.7534	Intermediate Similarity	NPC311973
0.75	Intermediate Similarity	NPC290582
0.75	Intermediate Similarity	NPC217748
0.75	Intermediate Similarity	NPC182052
0.75	Intermediate Similarity	NPC271013
0.75	Intermediate Similarity	NPC42663
0.75	Intermediate Similarity	NPC15414
0.7432	Intermediate Similarity	NPC116465
0.7432	Intermediate Similarity	NPC223690
0.7432	Intermediate Similarity	NPC9532
0.7397	Intermediate Similarity	NPC279228
0.72	Intermediate Similarity	NPC254441
0.7105	Intermediate Similarity	NPC229373
0.7067	Intermediate Similarity	NPC239824
0.7051	Intermediate Similarity	NPC475479
0.7051	Intermediate Similarity	NPC323537
0.6944	Remote Similarity	NPC41376
0.6849	Remote Similarity	NPC603603
0.675	Remote Similarity	NPC24260
0.675	Remote Similarity	NPC485712
0.6709	Remote Similarity	NPC195538
0.6707	Remote Similarity	NPC480590
0.6625	Remote Similarity	NPC243454
0.6585	Remote Similarity	NPC10871
0.6506	Remote Similarity	NPC480586
0.65	Remote Similarity	NPC16357
0.65	Remote Similarity	NPC302245
0.6456	Remote Similarity	NPC274716
0.6456	Remote Similarity	NPC167116
0.6456	Remote Similarity	NPC609821
0.642	Remote Similarity	NPC212237
0.6375	Remote Similarity	NPC181796
0.6375	Remote Similarity	NPC290005
0.6375	Remote Similarity	NPC54654
0.6375	Remote Similarity	NPC7715
0.6375	Remote Similarity	NPC328155
0.6375	Remote Similarity	NPC222661
0.6375	Remote Similarity	NPC285931
0.6341	Remote Similarity	NPC611658
0.6235	Remote Similarity	NPC281581
0.6203	Remote Similarity	NPC475393
0.6164	Remote Similarity	NPC30779
0.6145	Remote Similarity	NPC249996
0.6094	Remote Similarity	NPC213206
0.6094	Remote Similarity	NPC188163
0.6094	Remote Similarity	NPC328750
0.6027	Remote Similarity	NPC317272
0.6027	Remote Similarity	NPC268503
0.6	Remote Similarity	NPC286119
0.6	Remote Similarity	NPC239584
0.5977	Remote Similarity	NPC485711
0.5952	Remote Similarity	NPC8836
0.5938	Remote Similarity	NPC314682
0.5789	Remote Similarity	NPC256012
0.5789	Remote Similarity	NPC610965
0.5775	Remote Similarity	NPC104196
0.5682	Remote Similarity	NPC206900
0.5682	Remote Similarity	NPC11296
0.5682	Remote Similarity	NPC274661
0.5679	Remote Similarity	NPC608819
0.5667	Remote Similarity	NPC41122
0.5667	Remote Similarity	NPC318805
0.5625	Remote Similarity	NPC480591
0.561	Remote Similarity	NPC112248
0.5506	Remote Similarity	NPC82457
0.55	Remote Similarity	NPC240841
0.5495	Remote Similarity	NPC475597
0.5465	Remote Similarity	NPC139783
0.5465	Remote Similarity	NPC65312
0.5465	Remote Similarity	NPC611798
0.5402	Remote Similarity	NPC275680
0.5402	Remote Similarity	NPC22115
0.5349	Remote Similarity	NPC302275
0.5316	Remote Similarity	NPC480592
0.5269	Remote Similarity	NPC48490
0.5213	Remote Similarity	NPC608576
0.5165	Remote Similarity	NPC254581
0.5143	Remote Similarity	NPC185838
0.5139	Remote Similarity	NPC135538
0.5139	Remote Similarity	NPC24233
0.5106	Remote Similarity	NPC234318
0.5059	Remote Similarity	NPC600054
0.5059	Remote Similarity	NPC601504

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC12036 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5117
0.1-0.2	3929
0.2-0.3	88
0.3-0.4	10
0.4-0.5	2
0.5-0.6	0
0.6-0.7	1
0.7-0.8	1
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9516	High Similarity	NPD8099	Discontinued
0.8657	High Similarity	NPD8156	Discontinued
0.7746	Intermediate Similarity	NPD8095	Phase 1
0.6094	Remote Similarity	NPD4664	Clinical (unspecified phase)

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