NPASS Compound

Natural Product: NPC481744

Natural Product ID	NPC481744
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	PCONVUFXNJIGJM-YGYZOSCRSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic 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 96101 0 0 0 0 0 0 0 0999 V2000 9.0994 4.6921 -0.0941 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6128 3.3353 -0.4735 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0518 2.3292 0.5265 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5523 2.3855 0.4380 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0108 1.3862 1.4380 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5183 1.4521 1.3349 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7601 0.4447 1.0145 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2997 0.5374 0.9206 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5857 -0.5349 0.5879 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0834 -0.4986 0.4768 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5157 -0.7943 1.6818 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8169 -0.4511 1.4424 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.3239 -1.6882 0.6513 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.1847 -2.8373 1.5516 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4225 -4.1485 1.2519 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7391 -5.1491 2.3833 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7553 -6.1547 2.2410 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7392 -4.7246 -0.0618 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8836 -3.7438 -1.1825 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.6138 -2.9860 -1.3252 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2138 -3.0209 -2.7241 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9831 -3.8864 -3.3646 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9150 -4.2307 -4.8127 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9403 -4.4971 -2.4598 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6873 -5.4715 -2.6774 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6044 -1.6400 -0.6455 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3040 -0.5655 -1.4450 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.6647 -0.2486 -2.7583 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4437 0.7276 -0.6647 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.6843 0.7507 0.6256 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9546 1.9859 1.3794 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2717 2.0266 2.6282 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8419 3.3256 0.6753 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6903 0.8046 0.2406 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8086 1.0300 -0.4293 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4582 2.1092 -1.0047 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7882 2.8527 -1.7852 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8633 2.4844 -0.8000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6284 1.6035 0.1287 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0471 2.1242 0.2234 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0944 3.5382 0.7455 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4865 3.6324 2.1358 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7368 -1.3012 -0.5676 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0392 -2.9958 -1.1107 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8649 -5.5141 0.0264 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0790 -3.6655 1.4819 O 0 0 0 0 0 0 0 0 0 0 0 0 9.2140 4.8048 1.0089 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0459 4.7594 -0.4325 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7142 5.4513 -0.6370 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3327 3.0589 -1.4939 H 0 0 0 0 0 0 0 0 0 0 0 0 10.7265 3.2896 -0.3623 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3646 1.2957 0.2501 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3560 2.5465 1.5477 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1595 3.3836 0.7785 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1633 2.0987 -0.5572 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4092 0.3783 1.3380 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2420 1.7902 2.4576 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0502 2.3994 1.5407 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2259 -0.5053 0.8064 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7469 1.4448 1.1106 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1316 -1.4378 0.4002 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3779 -0.3872 2.3754 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4141 -1.4605 0.5271 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3810 -2.5441 2.6426 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7501 -5.5423 2.3038 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5102 -4.6666 3.3553 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1496 -7.0524 2.2953 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8871 -5.4085 -0.3509 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2118 -3.5750 -0.8074 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5591 -2.4864 -3.2420 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1639 -3.6288 -5.3503 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9211 -4.1273 -5.3001 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6499 -5.3073 -4.8619 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3622 -0.8726 -1.6977 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0155 0.8000 -3.0309 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0991 -0.8332 -3.6103 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4196 -0.1643 -2.7549 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0591 1.5542 -1.2969 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3866 1.2046 3.2997 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4577 3.0108 3.1122 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1377 3.9381 1.3053 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8249 3.7955 0.6868 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4423 3.2285 -0.3410 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8617 3.5574 -0.4835 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3407 2.4930 -1.8222 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6876 0.5936 -0.3507 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1230 1.5539 1.0971 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6066 1.4627 0.8847 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4438 2.1622 -0.8249 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6900 4.2818 0.0547 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1894 3.7882 0.8606 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4052 3.8952 2.1056 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6112 2.6971 2.6844 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0039 4.4438 2.6919 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7844 -3.5243 -1.4401 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7071 -6.4478 -0.3170 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 1 0 6 7 2 0 7 8 1 0 8 9 2 0 10 9 1 1 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 1 16 17 1 0 15 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 22 24 1 0 24 25 2 0 20 26 1 0 26 27 1 0 27 28 1 0 27 29 1 0 29 30 1 0 30 31 1 1 31 32 2 0 31 33 1 0 30 34 1 0 29 35 1 0 35 36 1 0 36 37 2 0 36 38 1 0 38 39 1 0 39 40 1 0 40 41 1 0 41 42 1 0 26 43 1 1 19 44 1 1 18 45 1 0 15 46 1 0 34 10 1 0 43 10 1 0 30 12 1 0 26 13 1 0 46 14 1 0 24 19 1 0 1 47 1 0 1 48 1 0 1 49 1 0 2 50 1 0 2 51 1 0 3 52 1 0 3 53 1 0 4 54 1 0 4 55 1 0 5 56 1 0 5 57 1 0 6 58 1 0 7 59 1 0 8 60 1 0 9 61 1 0 12 62 1 1 13 63 1 6 14 64 1 1 16 65 1 0 16 66 1 0 17 67 1 0 18 68 1 6 20 69 1 1 21 70 1 0 23 71 1 0 23 72 1 0 23 73 1 0 27 74 1 6 28 75 1 0 28 76 1 0 28 77 1 0 29 78 1 6 32 79 1 0 32 80 1 0 33 81 1 0 33 82 1 0 33 83 1 0 38 84 1 0 38 85 1 0 39 86 1 0 39 87 1 0 40 88 1 0 40 89 1 0 41 90 1 0 41 91 1 0 42 92 1 0 42 93 1 0 42 94 1 0 44 95 1 0 45 96 1 0 M END

Standard InCHIKey	PCONVUFXNJIGJM-YGYZOSCRSA-N
Standard InCHI	InChI=1S/C36H50O10/c1-7-9-11-12-13-14-16-18-33-44-30-26-29-32(20-37,43-29)31(40)34(41)24(19-22(5)27(34)39)36(26,46-33)23(6)28(35(30,45-33)21(3)4)42-25(38)17-15-10-8-2/h13-14,16,18-19,23-24,26,28-31,37,40-41H,3,7-12,15,17,20H2,1-2,4-6H3/b14-13+,18-16+/t23-,24-,26+,28-,29+,30-,31-,32+,33-,34-,35+,36+/m1/s1
SMILES	CCCCC/C=C/C=C/[C@@]12O[C@@H]3[C@@H]4[C@H]5[C@@](CO)([C@H]([C@]6([C@@H](C=C(C)C6=O)[C@]4([C@H](C)[C@H]([C@]3(C(=C)C)O1)OC(=O)CCCCC)O2)O)O)O5

Calculated Properties

Physi-Chem Properties

Molecular Weight:	642.34	Volume:	651.957 ? Van der Waals volume.
Dense:	0.985	LogP:	4.446 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.302 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.8 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	14.0	Rigid Bonds:	29.0
TPSA:	144.28 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	3.0	Rings:	6.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.089	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.814	Fsp³:	0.722
MCE-18:	105.032 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.519	Fluc inhibitor:	0.063 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.005 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.01 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.155	Promiscuous compounds:	0.474

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.298	MDCK Permeability:	-4.933
Pgp-inhibitor:	0.015	Pgp-substrate:	0.035
PAMPA:	0.048 ? 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):	0.004
20% Bioavailability (F20%):	0.305	30% Bioavailability (F30%):	0.978
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.069	MRP1:	0.906
Plasma Protein Binding (PPB):	96.858%	Volume Distribution (VD):	-0.009
Fu:	2.723% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.993
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.085
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.931
CYP2C19-inhibitor:	0.009	CYP2C19-substrate:	0.974
CYP2C9-inhibitor:	0.014	CYP2C9-substrate:	0.009
CYP2D6-inhibitor:	0.05	CYP2D6-substrate:	0.022
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.999
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.381 ? 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):

4.341

Half-life (T1/2):

0.872

ADMET: Toxicity

hERG Blockers:	0.128	hERG Blockers (10um):	0.418
Human Hepatotoxicity (H-HT):	0.444	Drug-induced Liver Injury (DILI):	0.22
AMES Toxicity:	0.834	Rat Oral Acute Toxicity:	0.615
Maximum Recommended Daily Dose:	0.52	Skin Sensitization:	1.0
Carcinogencity:	0.258	Eye Corrosion:	0.047
Eye Irritation:	0.659	Respiratory Toxicity:	0.902
Drug-induced Neurotoxicity:	0.104	Ototoxicity:	0.8
Hematotoxicity:	0.752	Drug-induced Nephrotoxicity:	0.566
Genotoxicity:	0.005	RPMI-8226 Immunitoxicity:	0.27
A549 Cytotoxicity:	0.783	Hek293 Cytotoxicity:	0.658
BCF:	1.574 ? 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:	4.556 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.946 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.43 ? 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
NPO9756	Daphne genkwa	Species	Thymelaeaceae	Eukaryota	n.a.	flower	n.a.	PMID[21916433]
NPO9756	Daphne genkwa	Species	Thymelaeaceae	Eukaryota	flower buds	n.a.	n.a.	PMID[23558238]
NPO9756	Daphne genkwa	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27228307]
NPO9756	Daphne genkwa	Species	Thymelaeaceae	Eukaryota	Roots	n.a.	n.a.	PMID[31150241]
NPO9756	Daphne genkwa	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31860304]
NPO9756	Daphne genkwa	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32223193]
NPO9756	Daphne genkwa	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9756	Daphne genkwa	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9756	Daphne genkwa	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO9756	Daphne genkwa	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO9756	Daphne genkwa	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO9756	Daphne genkwa	Species	Thymelaeaceae	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	1
Ratio CC50/IC50	1
CC50	1

Activity Type	# Activity
Cell line	1
Organism	1
Others	1

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
NPT25	Cell line	MT4	Homo sapiens	CC50	>	6200.0	nM	PMID[31860304]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	IC50	<	0.8	nM	PMID[31860304]
NPT2	Others	Unspecified	n.a.	Ratio CC50/IC50	>	7987.0	n.a.	PMID[31860304]

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 NPC481744 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	18510
0.1-0.2	29692
0.2-0.3	1533
0.3-0.4	49
0.4-0.5	19
0.5-0.6	10
0.6-0.7	10
0.7-0.8	0
0.8-0.85	3
0.85-0.9	5
0.9-0.95	7
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.973	High Similarity	NPC481743
0.9595	High Similarity	NPC39509
0.92	High Similarity	NPC75831
0.92	High Similarity	NPC471137
0.9067	High Similarity	NPC223356
0.9067	High Similarity	NPC298697
0.9067	High Similarity	NPC475500
0.9067	High Similarity	NPC100017
0.9067	High Similarity	NPC481742
0.8947	High Similarity	NPC182266
0.8947	High Similarity	NPC475154
0.8947	High Similarity	NPC485700
0.8831	High Similarity	NPC471136
0.8831	High Similarity	NPC116727
0.8312	Intermediate Similarity	NPC324104
0.8312	Intermediate Similarity	NPC473548
0.8205	Intermediate Similarity	NPC180902
0.7556	Intermediate Similarity	NPC101786
0.75	Intermediate Similarity	NPC251564
0.75	Intermediate Similarity	NPC477189
0.7416	Intermediate Similarity	NPC92598
0.7416	Intermediate Similarity	NPC43304
0.7416	Intermediate Similarity	NPC481753
0.7416	Intermediate Similarity	NPC477188
0.7416	Intermediate Similarity	NPC477190
0.7407	Intermediate Similarity	NPC474508
0.7407	Intermediate Similarity	NPC473485
0.7407	Intermediate Similarity	NPC171411
0.7407	Intermediate Similarity	NPC485701
0.7391	Intermediate Similarity	NPC481773
0.7195	Intermediate Similarity	NPC475314
0.7195	Intermediate Similarity	NPC102997
0.7108	Intermediate Similarity	NPC485693
0.6957	Remote Similarity	NPC130886
0.6957	Remote Similarity	NPC486153
0.6813	Remote Similarity	NPC164150
0.6813	Remote Similarity	NPC481754
0.6809	Remote Similarity	NPC481774
0.68	Remote Similarity	NPC69240
0.6627	Remote Similarity	NPC162495
0.6548	Remote Similarity	NPC475606
0.6383	Remote Similarity	NPC68282
0.6275	Remote Similarity	NPC191992
0.587	Remote Similarity	NPC475139
0.5591	Remote Similarity	NPC473838
0.5556	Remote Similarity	NPC481745
0.54	Remote Similarity	NPC486154
0.5312	Remote Similarity	NPC605479
0.5227	Remote Similarity	NPC475273
0.5227	Remote Similarity	NPC168849
0.5227	Remote Similarity	NPC217901
0.5227	Remote Similarity	NPC611341
0.5158	Remote Similarity	NPC481750

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC481744 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6799
0.1-0.2	2310
0.2-0.3	41
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